Dimethyl fumarate / Monomethyl fumarate – USA

On Jan 07, 2020, Chief Judge Leonard P. Stark of Delaware granted motion under Rule 12(c) for judgment on the pleadings for non-infringement to Baner Life Sciences.

Plaintiff Biogen International GmbH owns U.S. Patent No. 7,619,001 which is listed in OB for Tecfidera® (Dimethyl fumarate). US’001 patent originally set to expire on April 1, 2018 but Biogen filed PTE and thus term extended till June 20, 2020. On January 18, 2018, Banner submitted NDA under§ 505(b)(2), seeking approval for Bafiertam (monomethyl fumarate "MMF") delayed-release capsules for the treatment of Multiple Sclerosis. Banner received tentative approval from the FDA on November 16, 2018. Biogen sued Banner for infringement of the '001 Patent on December 27, 2018 within 45 days & obtained an automatic 30-month stay of FDA approval of Banner's Bafiertam product. Thus, at this time, the only impediment to Banner obtaining final FDA approval and having the right to market Bafiertam is the pendency of this litigation. Banner then moved under Rule 12(c) for judgment on the pleadings on the basis of non-infringement, reasoning that the '001 Patent's extension does not cover Banner's tentatively-approved product.

Relevant claims at issue here are claim 1 & claim 5:

1. A method of treating multiple sclerosis comprising administering ... an amount of a pharmaceutical preparation effective for treating multiple sclerosis, the pharmaceutical preparation comprising ... dimethyl fumarate [DMF], methyl hydrogen fumarate [MMF], or a combination thereof.

5. The method of claim 1, the pharmaceutical preparation comprising methyl hydrogen fumarate [MMF].

Court’s analysis:

Banner contended that the portion of the '001 patent that Bafiertam practices expired in April 2018. In Banner's view, Biogen's PTE applies only to the claimed embodiment which constitutes Biogen's FDA-approved DMF product, Tecfidera. The '001 patent was only extended, and can only be enforced, with respect to a DMF-containing product. Because Banner's Bafiertam contains MMF and not DMF, Banner argued it is entitled to judgment on the pleadings of no infringement.

The parties were in agreement that Biogen successfully obtained a PTE on its ' 001 patent until June 20, 2020 based on its FDA-approved product, Tecfidera. The parties disagree, however, on the scope of that extension and, particularly, whether it extends to Banner's MMF product. Court said that PTE extends the term of entire patent & not claim-by-claim basis. This does not mean, however, that Biogen, has the right to enforce the entirety of the ' 001 patent. Rather, § 156(b)2 limits the effect of the extension to the "rights derived'' under§ 156(a). Subsection 156(b)(2) limits the "rights derived" from a PTE "to any use [i] claimed by the patent and [ii] approved for the product." Under this reasoning, the '001 patent rights that Biogen may enforce during the extension period are limited to a method of treating MS using DMF (not MMF). On the contrary, Biogen reads§ 156(b)(2) as not just limited to the specific FDA-approved product/use combination (in this case, Tecfidera (DMF) for MS), but as also reaching any claim (or any portion of any claim) in the '001 patent directed to methods of treating MS. Thus, under Biogen's interpretation, the PTE applies to any drug product disclosed in the claimed methods of the '001 patent that can be used to treat MS, which in this case, would include the use of DMF, MMF, or any salts or esters thereof. Court, however, agreed with Banner's view as to the meaning of 156(b)(2).

Specifically, court said that pursuant to 35 U.S.C. 156(b), if the patent claims other products in addition to the approved product, the exclusive patent rights to the additional products expire with the original expiration date of the patent. In other words, the "rights derived" from the PTE do not extend to all embodiments within the scope of the claims that have been extended. Instead, those rights extend only to the claimed embodiment on which the extension is based, i.e., the FDA-approved drug product. Now therefore, the pertinent question here is: what is the "active ingredient" of Biogen's approved drug product, Tecfidera?  Is it dimethyl fumarate or monomethyl fumarate? (Dimethyl fumarate gets converted into monomethyl fumarate in the body which is an active form).

Banner argued that the "active ingredient" is the molecule found in the administered drug product before it is administered to the patient. Therefore, to Banner, the "active ingredient" of Tecfidera is DMF. Biogen, however, contends that Tecfidera's active ingredient is the active moiety, which here is MMF (as well as salts and esters of MMF). Both parties put forth reasonable interpretations of the statutory framework in light of two precedential Federal Circuit cases. Banner relies on Judge Michel's opinion in Glaxo Operations UK Ltd. v. Quigg, 894 F.2d 392 (Fed. Cir. 1990), which held that "active ingredient" refers to the molecule in the drug product to be administered, not the active moiety; while Biogen relies on Judge Newman's opinion in Pfizer v. Dr. Reddy 's Laboratories, 359 F.3d 1361 (Fed. Cir. 2004); which held that "active ingredient" for purposes of the PTE is active moiety in the body. However, in PhotoCure ASA v. Kappos, 603 F.3d at 1375, the Federal Circuit stated that its Glaxo and Pfizer decisions "are not in conflict." The Federal Circuit quoted Glaxo and reaffirmed that "a compound can only qualify as the 'active ingredient' of a drug if that compound itself is present in the drug." Further, PhotoCure emphatically states: "Pfizer did not change the law of§ 156." Rather, the Federal Circuit explained that "[t]he issue in Pfizer was whether infringement of an extended patent ... was avoided by changing the salt," and Pfizer's holding was that one cannot avoid infringement of an extended patent term simply by changing the salt of the active moiety.

Court said that given the Federal Circuit's instruction that there is no direct conflict between Glaxo and Pfizer, it must, consistent with Glaxo and the unambiguous meaning of§ 156(f)(2), look for the "active ingredient" of Biogen's FDA-approved product in that product at the time of administration, before the product is taken by a human patient. Here, the FDA-approved product that is the basis for the ' 001 patent's PTE is Biogen's Tecfidera. It is undisputed that the "active ingredient" in Tecfidera when administered (i.e., before it is ingested by a human patient) is DMF. Therefore, Biogen's enforceable, extended patent rights extend only to DMF. While DMF is an ester of MMF, MMF is neither a salt nor ester of DMF. Therefore, by operation of §156(b)(2) and 156(f)(2), Biogen has no enforceable rights during the patent extension period with respect to MMF. Thus, Court granted Banner's motion for judgment on the pleadings of non infringement.