To satisfy the written description requirement under 35 U.S.C. 112, a patent specification must describe the claimed invention in such sufficient detail that a person of skilled in the art (POSA) can reasonably conclude that the inventor had possession of the claimed invention. In Biogen International GmbH v. Mylan Pharmaceuticals Inc., at issue is whether the specification provides adequate written description for method of use claims¹ to a specific dosage strength, 480 mg/day, of dimethyl fumarate (DMF480). On November 30, 2021, in a split decision, the Federal Circuit affirmed the district court decision finding the method claims of the ‘514 patent invalid for lack of written description.

Biogen conducted a Phase II clinical trial from 2004-2006 “to test the efficacy of DMF at 120, 360 and 720 mg/day” dosages to treat multiple sclerosis (MS).² A May 2006 readout of the Phase II trials demonstrated the 720 mg/day dosage strength was efficacious to treat multiple sclerosis, but the other two strengths were not.³ In August 2006, FDA recommended Biogen add a DMF480 dosage to the Phase III clinical trial “because the lower dose might improve patient compliance and/or minimize dropouts from adverse effects during the clinical study.”⁴ According to Biogen, the DMF480 dose was not included in the Phase II trial for “commercial reasons,” although the Phase II trial lead scientist had “advocated testing the DMF480 dose as part of the trial in February 2004” and “conceived the idea of using DMF480 as early as 2003.”⁵

In February 2007, Biogen filed a provisional patent application⁶ based on the 2006 Phase II data.⁷ The effective dosage “from about 480 mg to about 720 mg per day” was disclosed in the provisional patent application.⁸ The specification states “[t]he 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.”⁹

Biogen conducted a Phase III clinical trial from 2007-2011. The readout of the Phase III clinical trial demonstrated that both DMF480 and DMF720 were efficacious.¹⁰ Following the Phase III trial, Biogen amended the ‘921 Application changing the title to “Treatment for Multiple Sclerosis” and named the clinical trial researcher as an inventor.¹¹ No changes were made to the specification.¹²

The majority stated “[t]he core issue in this appeal is whether the specification Biogen filed on February 8, 2007 supports the 2011 claims that issued in the ’514 Patent. Even more precisely, the narrow ground on which this question turns is whether the original specification demonstrates ‘possession’ of the claimed therapeutically effective DMF480-dose limitation to treat MS.”¹³ The Court noted the POSA would “look in the specification for guidance vis-à-vis a suitable therapeutic-DMF dosage.…The DMF480 dose is listed only once in the entire specification.”¹⁴ The Court also noted the disclosure of DMF480 “appears at the end of one range among a series of ranges,” and “broad DMF-dosage ranges show that the inventors did not possess a therapeutically effective DMF480 dose at the time of filing in 2007.”¹⁵ The majority further noted the written-description analysis rests on the disclosure at time of filing before the Phase III data was available, not whether “Biogen later established the therapeutic efficacy of DMF480.”¹⁶

The majority held “[t]he written-description requirement limits patent protection only to individuals who perform the difficult work of producing a complete and final invention featuring all its claimed limitations and publicly disclose the fruits of that effort.”¹⁷ In affirming the district court’s decision finding the ‘514 patent invalid for lack of written description, the majority determined the district court did not clearly err in finding a POSA “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.”¹⁸ The majority noted that weighing the credibility of the inventor and expert witness testimony, “[a]t the conclusion of the trial, the district court found that the specification did not reasonably convey to a POSA that the ’514 Patent inventors had ‘actually invented’ a method of treating MS with a therapeutically effective dose of DMF480” as of the ‘921 Application filing date.”¹⁹

In a strong dissent, Justice O’Malley stated that while she is “loath to reverse district court determinations that rely heavily on credibility findings,” the district court erred, thus the case should be reversed and remanded.²⁰ The dissent noted that “[s]omewhat circularly, after acknowledging that clinical data demonstrating effectiveness is not required to satisfy written description, the district court went on to find that the ’514 patent does not demonstrate possession because it lacks clinical efficacy data.”²¹

Biogen’s Brief

On December 30, 2021, Biogen filed a Combined Petition for Panel Rehearing and Rehearing En Banc. In its brief, Biogen sets forth the following questions:

    1. Does 35 U.S.C. § 112’s requirement to provide “a written description of              the invention” require that the specification prove the invention’s                      efficacy?
   2. Does a specification that discloses multiple embodiments have to                       repeatedly describe and single out the claimed embodiment?
   3. May a court of appeals defer to a district court’s factfinding while                       declining to address multiple legal errors that skewed that factfinding 22

Biogen argues that the majority “departs from precedent and 35 U.S.C. § 112’s plain text requiring a written description of the invention,” and instead requires that the specification itself “prove the described effect.”²³ Biogen points out that there is no dispute the ‘514 patent specification listed four nested DMF dose ranges including 480 mg to about 720 mg per day, the DMF480 dose was specifically disclosed and “[t]he panel majority’s insistence on further repetition or singling out [of the DMF480 dose], if allowed to stand, would have far-reaching consequences.”²⁴ In requesting the Court grant panel or en banc rehearing, Biogen argues the panel majority failed to address legal errors from the district court that “had a significant impact on its written description finding.”²⁵ Likewise, Biogen argues the majority decision imposes a heightened standard that “creates a Catch-22: a patent application must be filed before [Phase III] clinical trials to avoid the risk of invalidation for anticipation or obviousness, but then is at risk of invalidation for lack of written description for not including data from those same clinical trials.”²⁶

Amicus Briefs

On January 13, 2022, amicus briefs were filed by interested parties, Pharmaceutical Research and Manufacturers of America (PhrMA) and Biotechnology Innovation Organization (BIO) in support of panel rehearing and rehearing en banc, and the Chemistry and the Law Division of the American Chemical Society (CHAL) in support of rehearing en banc and reversal.

PhrMA argues the majority decision upholding the district court essentially requires Phase III clinic data in the disclosure and “if left undisturbed, could diminish the patent incentive for innovators to conduct research and development of new methods of treatment using known and otherwise unpatentable compounds.”²⁷ PhrMA further argues the majority’s decision demands “far more than what was needed to describe the therapeutic method claimed here—clinical evidence that the claimed method worked. That cannot be justified under the law governing written description.”²⁸ PhrMA brief also notes it has been “long-established” that the disclosure “need not demonstrate that a claimed human therapy is safe or fully effective to demonstrate it has practical utility.”²⁹ PhrMA also notes that the majority “criticized the prophetic nature of the patent’s disclosure of the DMF480 dose,” yet Federal Circuit precedent recognizes “a patent application is not required to include actual working examples of the invention to describe or enable a therapeutic invention.”³⁰

In its amicus brief, BIO expresses concern that the majority decision is “creating a heightened standard for written description under 35 U.S.C. § 112 that may cause unintended harm” to companies represented by the BIO trade association.³¹ BIO argues the specification of the ‘514 patent explicitly discloses the nested range “from about 480 mg to about 720 mg per day” and “teaches potential dosage levels for DMF monotherapy in a single paragraph.”³² BIO also notes the quandary innovator drug companies would face under such a heightened standard for written description: drug companies may need to disclose details about a Phase III clinical trial to recruit patients, if these data need to be disclosed to meet the written description requirement and patent applications cannot be filed before such a disclosure needs to be made, such a requirement can chill innovation, particularly for smaller companies.³³

CHAL argues the “majority’s decision departs from precedent and 35 U.S.C. § 112’s plain text requiring a written description of the invention, and instead requires that the specification itself prove the described effect, which would require that the written description requirement mandated actual reduction to practice of the invention.”³⁴ It further argues “whether an invention works, or whether the dosage had been demonstrated to be effective, is not the test for sufficiency of a description of an invention. The patent clearly expresses a range of effective dosages, including the dosage at issue in this appeal.”³⁵

Takeaways:

Biogen is problematic for patent owners facing invalidity challenges based on lack of written description. If the decision is left undisturbed, disclosure of nested dosage ranges and prophetic examples in the specification may not suffice to overcome a written description challenge absent proof the dosage has a therapeutic effect based on actual Phase III data. However, if a clinical trial is conducted prior to filing the patent application, the clinical trial itself may be prior art to the patent, thereby creating a Catch-22 for innovators. Biogen suggests that listing possible therapeutic dosage multiple times throughout the specification may help to prove the appreciation of the efficacy of the dosage at filing and thus weigh in favor of showing possession.

For defendants challenging validity of dosing claims based on written description, as it stands Biogen may provide an argument that absence of clinical trial data, even for nested dosage ranges, may be sufficient to find a patent invalid for lack of written description.

Whether a claim meets the written description standard is a question of fact with a clear error standard of review. Because the trier of fact must weigh the credibility of the witness testimony and written description challenge are often highly fact specific, Biogen also demonstrates the importance of direct and cross-examination trial testimony of inventors and expert witnesses on behalf of both patent owners and challengers.

¹ See, e.g., Claim 1 of U.S. Patent No. 8.399,514 (‘514 patent).
² Biogen at 9.
³ Id.
⁴ Id. (cleaned up).
⁵ Id.
⁶ U.S. Provisional Application 60/888,921 (‘921 Application) was filed on February 8, 2007.
⁷ Biogen at 9.
⁸ ‘514 patent, col. 18 ll. 54-64 (emphasis added).
⁹ Id. at col. 5 ll. 52-59.
¹⁰ Biogen at 9.
¹¹ Id. at 7, 9.
¹² Id. at 10.
¹³ Id. at 14.
¹⁴ Id. at 16.
¹⁵ Id.
¹⁶ Id. at 17.
¹⁷ Id. at 18.
¹⁸ Id.
¹⁹ Id. at 11.
²⁰ Id., Dissent at 1.
²¹ Id., Dissent at 6.
²² Biogen’s Brief at 1.
²³ Id. at 3-4. (cleaned up).
²⁴ Id. at 15.
²⁵ Id. at 16-18.
²⁶ Id. at 14.
²⁷ PhrMA Brief at 12-13.
²⁸ Id. at 4.
²⁹ Id. at 7. (cleaned up).
³⁰ Id. at 10-11.
³¹ Bio Brief at 1.
³² Id. at 3. (citations omitted.)
³³ Id. at 8-9.
³⁴ CHAL Brief at 3.
³⁵ Id. at 5. (cleaned up).