Dimethyl fumarate – USA

On Oct 24, 2018, Federal Circuit affirmed Patent Trial and Appeal Board’s decision that Forward pharma’s MS treatment claim is not supported by adequate written description. 

This appeal arises from an interference proceeding at Patent Trial and Appeal Board and involves a treatment method for multiple sclerosis with a particular daily dosage—480 mg—of fumaric acid esters. Appellee Biogen MA, Inc. (Biogen) owns U.S. Patent No. 8,399,514, which describes and claims this method of treatment. The US’514 claims priority to a provisional application filed on February 8, 2007. Appellant FWP IP ApS (Forward) is the assignee of U.S. Patent Application No. 11/576,871, which discloses controlled release compositions of fumarates. The US’871 claims priority to a Danish patent application filed on October 8, 2004. Forward argues that its patent application describes the specific treatment method in dispute. While the Board found that Forward’s ’871 application had an earlier priority date than Biogen’s ’514 patent, it granted Biogen’s motion for judgment that the MS treatment claims of US’871 application are not supported by adequate written description under 35 U.S.C. § 112.

The Board found that the ’871 application’s focus on “controlled release fumarate compositions” and “general teaching of applicability of the fumarates to the treatment of a variety of possible disease or conditions and the teaching of a broad range of possible dosages would not have conveyed possession of the specific treatment of MS that Forward now claims.” Reviewing the ’871 application’s specification, the Board found that the principal focus of the disclosure is the minimization of gastro-intestinal side-effects through the use of controlled release of fumarates. As to the treatment of specific diseases and conditions, the Board found that Forward’s specification lists over twenty diseases and conditions, and MS is not identified as of any particular interest. The only diseases that the ’871 application discusses in any detail, however, are psoriasis and conditions associated with psoriasis. The two commercial compositions of fumarates the specification identifies are Biogen’s Fumaderm® and TioFarma’s Fumaraat 120®, both of which can be used for treating psoriasis. With respect to the fumarate content, the Board found that, while the ’871 application’s specification teaches the active ingredient can be any fumarate, it does separately identify DMF, MMF, and their combination for use in treatment formulations such that a skilled artisan would have recognized that the inventors had considered those fumarates to be significant. The daily dosage paragraph teaches that the dosage can be from 240 to 360 mg, 360 to 480 mg, 480 to 600 mg, 600 to 720 mg, 720 to 840 mg, 840 to 960 mg, or 960 to 1080 mg, given in one to three administrations. The 480 mg/day dose thus is identified as both the low and high end of ranges within a broader, overall disclosed dosage range of 240 to 1080 mg/day. While 480 mg/day dosage is expressly mentioned three times in the specification, the Board found that there “is no discussion that would guide one skilled in the art to treat MS with a therapeutically effective dose of 480 mg/day, or any other therapeutically effective dose within the ranges disclosed. Thus, the Board concluded that Forward’s claims 55– 70 failed to meet the written description requirement. The Board found that, even though each required claim element is mentioned separately in Forward’s specification, the specification did not disclose the claimed invention in a manner that adequately describes the now claimed MS treatment to a skilled artisan. Forward appealed.

On appeal, Forward argued that the upscale table (1) discloses a 480 mg/day dosage, (2) is reasonably directed at using DMF to treat the listed conditions, and (3) is linked to the treatment of MS. And at oral argument, Forward again asserted that the kits for administration of fumarates over the up-titration schedule (up-scale table) tie together the dose, drug, and disease. Forward contends that the up-scale table in the ’871 application expressly discloses this 480 mg/day dosage during the seventh week of a contemplated nine-week scale-up period. Forward argued, POSA would have recognized that all of the listed dosages in that nine-week up-scale table are therapeutically effective dosages for all of the conditions and diseases listed elsewhere in the specification. Federal Circuit, however not persuaded & agreed with Board that the up-scale table does not discuss therapeutically effective dosages at all, much less the specific dosage of 480 mg of fumarates per day as being therapeutically effective for treating MS. Rather, the up-scale table as simply providing guidance on gradual dosing over a period of several weeks to help patients’ gastro-intestinal systems acclimate to the side-effects of fumarates. The 480 mg/day disclosure in week seven is an interim dosage, and Forward has not presented persuasive evidence why a skilled artisan would have understood the week seven interim dosage to be therapeutically effective. On the other hand, Biogen’s expert testified that, because MS is a chronic disease, a skilled artisan would not have viewed a one week, interim dosage in the middle of a nine week up-scale schedule as an adequate treatment dosage, let alone one for a particular disease, such as MS. Substantial evidence supports the Board’s finding that Forward’s ’871 application lacks adequate written description support for the claimed treatment method. Moreover, a person of ordinary skill in the art reading [the ’871 application] would not have expected that a dose of an agent for potentially treating one of the many listed non-neurological diseases would also treat a neurological disease such as MS.”

Forward next tried to rely on the prior art for establishing a prior, known link between MS and fumarates. But Federal Circuit held that the prior art does not teach the key limitation of the count: the 480 mg daily dosage. Biogen counter argued that it was only during its phase 3 clinical trials when it confirmed that 480 mg/day of DMF is effective for treating MS. Lastly, Forward argued that the ’871 application’s original claims—which it canceled and replaced with new claims to provoke the interference proceeding— adequately describe the MS treatment it now seeks to claim. Federal Circuit sided with Board & held that Board correctly observed that a skilled artisan would need to pick and choose from Forward’s claims without any guidance from the written description. Forward provides no explanation as to why a skilled artisan would be able to cobble together selected elements from several different claims and thus recognize the now-claimed 480 mg/day of DMF and/or MMF for the treatment of MS from these 45 claims covering a broad scope of subject matter.

Thus, Federal Circuit affirmed Board’s finding that the MS treatment Forward now claims is not supported by adequate written description under 35 U.S.C. § 112.