No Clear Error to Find Lack of Written Description for a Method of Treatment Patent Despite Separate Disclosures of the Drug, Disease, and Dose (as Part of a Range)

December 29, 2021

Biogen International GMBH, Biogen MA, Inc., v. Mylan Pharmaceuticals Inc. marks the Federal Circuit’s most recent interpretation of the 35 U.S.C. § 112 written description requirement in the Hatch-Waxman context. No. 2020-1933, 2021 U.S. App. LEXIS 35254 (Fed. Cir. Nov. 30, 2021). Despite the specification containing explicit disclosures of the claimed drug, disease, and dose (but only as a part of a range), the Federal Circuit affirmed a district court’s finding that Biogen’s method of treatment claims lacked written description.

I. The District Court Finds Lack of Written Description

Biogen concerned U.S. Patent 8,399,514 (the ’514 patent), which claimed a method of treating multiple sclerosis (MS) using “a therapeutically effective amount of dimethyl fumarate” (DMF) of about 480 milligrams per day. Id. at *6-7. Biogen markets dimethyl fumarate under the brand name Tecfidera®. Id. at *7. The ’514 patent claimed priority back to a provisional application that was filed February 8, 2007. Id.

In 2017, Biogen filed suit in the Northern District of West Virginia when Mylan sought FDA approval for its generic dimethyl fumarate product. Id. at *13. In defense, Mylan contended that the ’514 patent lacked written description because a POSA would not have expected the 480 mg dose to provide clinically meaningful effectiveness when used to treat MS. Id. at *31. In response, Biogen emphasized that the claims only covered therapeutic effects, and thus Mylan had mischaracterized the written description needed to satisfy 35 U.S.C. § 112. See id. at *31-32. The district court, however, estopped Biogen from distinguishing clinical and therapeutic effectiveness, reasoning that it could not “deliberately change its position according to the exigencies of the moment.” Id. at *31 (citations omitted).

Following a four-day bench trial, the district court held that Mylan had shown by clear and convincing evidence that the asserted claims were invalid under 35 U.S.C. § 112 for lack of written description. Id. at *13. Specifically, the district court found that the ’514 patent specification did not reasonably convey to a person of ordinary skill in the art (POSA) that the “inventors had ‘actually invented’ a method of treating MS with a therapeutically effective dose of DMF480 as of February 8, 2007.” Id. at *14.

II. Facts Cited in the Majority’s Finding of No Clear Error

Focusing on the specification and finding no reason to disturb the district court’s credibility findings, the Federal Circuit affirmed. Id. at *29. The key issue on appeal was whether the specification adequately described possession of the therapeutically effective DMF480-dose limitation to treat MS, when viewed from the perspective of a POSA at the time of filing. Id. at *18. Even assuming that the specification adequately disclosed a method of treating MS, and that DMF may be used to treat MS, the majority found no clear error and identified a number of facts that informed it analysis. Id. at *19-24.

Overly Broad Specification: The specification casted “a wide net for a myriad of neurological disorders,” with MS being one of nearly three dozen disclosed disorders. Id. at *7, *18.

Specification Focused on Drug Discovery, Not Clinical Efficacy: The provisional application was originally titled “Nrf2 Screening Assays and Related Methods and Compositions,” and the specification focused on drug screening, discovery, and basic research. Id. at *7, *20. Dr. Lukashev, the original inventor, testified that his work was exploratory in nature, did not seek to inform the clinical dosing of DMF, and could not “be extrapolated to a clinical dose of DMF.” Id. at *12. (citations omitted).

Disclosed Doses Included Ineffective Doses: The specification contained only one paragraph disclosing DMF dosage ranges, including ranges from 100 to 1,000, 200 to 800, 240 to 720, and 480 to 720 mg per day. Id. at *7-9. But it also contained doses that were ineffective. Id. at *23-24. Thus, the only specific disclosure of the 480 mg dose was at the lower end of a particular range, amongst even broader ranges that included ineffective doses. Id. at *7-9.

Dose Not Linked to MS: The only paragraph disclosing DMF dosage ranges did not specify any particular neurological disorder. Id. Biogen’s expert, Dr. Wynn, “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.” Id. at *14. Mylan’s expert, Dr. Greenberg, also testified that the single paragraph disclosing the 480 mg dose did not “specifically link an effective dose of DMF to the treatment of MS.” Id. at *21.

No Clinical Data on Dose: As of the provisional filing date, the clinical implications of the Nrf2 pathway were unknown. Id. at *22. While a 720 mg dose was known to be effective, the Phase III study of DMF480 had not even commenced when the provisional was filed. Id. at *22.

Change of Title and Inventorship: It was not until 2011, after Biogen acquired Phase III clinical data for DMF480 in MS, that the invention’s title was changed to “Treatment for Multiple Sclerosis.” Id. at *8. This was also when Dr. O’Neill, the Phase II lead scientist, was listed as a coinventor, which suggests that Dr. O’Neill had not discovered the 480 mg dose as of the February 8, 2007 priority date. Id. at *12, *23.

III. The Dissent: Clinical Efficacy and Therapeutic Efficacy are Different Concepts

Judge O’Malley, dissenting, found the district court’s written description analysis tainted by its threshold error of applying judicial estoppel to prevent Biogen from distinguishing clinical and therapeutic efficacy. Id. at *29. Clinical efficacy “involves the type of scientific rigor associated with Phase III clinical trials: the investigative DMF480 dose must produce superior clinical endpoints to the standard of care for MS.” Id. at *30. Therapeutic efficacy, however, describes the amount of DMF that prevents or delays the onset, or ameliorates symptoms of, a neurological disorder and does not require efficacy on clinical endpoints. Id.

According to Judge O’Malley, the district court’s holding that judicial estoppel precluded Biogen from distinguishing clinical and therapeutic efficacy reflects the district court’s misunderstanding of what is claimed and what requires written description support. Id. at *32. In other words, the specification need only describe DMF’s ability to mitigate MS symptoms via Nrf2 expression to satisfy the written description requirement. It need not show that DMF outperforms the standard of care.

Judge O’Malley also found the district court’s failure to distinguish clinical and therapeutic efficacy caused it to erroneously conflate the concepts of obviousness and written description. Id. at *35. Despite acknowledging that data showing clinical efficacy is not required to satisfy the written description requirement, the district court effectively found a lack of written description for that very reason. See id. According to the district court, because Biogen defended against Mylan’s obviousness challenges “by contending that a POSA would not have expected the DMF480 dose to clinically treat MS, the ’514 patent’s failure to teach a POSA otherwise with clinical data dooms Biogen’s written description arguments.” Id. at *36. But written description only requires that a patent reasonably convey to a POSA “that the inventor had possession of the claimed subject matter as of the filing date.” Id.

Judge O’Malley went on to explain that what “a POSA would expect regarding clinical efficacy based on the prior art is a distinct question from whether a POSA would understand that the inventor possessed the claimed invention—i.e., a therapeutically effective dose—based on the patent’s written description.” Id. at *38. Accordingly, Judge O’Malley would have reversed and remanded for “a proper written description analysis that minds the gaps between obviousness and written description, as well as therapeutic and clinical efficacy.” Id. at *38.

IV. Conclusion

Biogen demonstrates the importance of developing factual support at trial for written description arguments under 35 U.S.C. § 112.