Delhi High Court Emphasizes the Importance of Claim Mapping in Patent Cases

Biogen fends off Mylan’s challenge

Dimethyl Fumarate, Proprietary molecule of Biogen with brand name as TECFIDERA available as delayed release capsule with two strength 120mg & 240mg.

USFDA has approved the New Drug Application (NDA 204063) provides for the use of Tecfidera (dimethyl fumarate) delayed-release capsules, 120 mg and 240 mg, for the treatment of patients with relapsing forms of multiple sclerosis.

OB Listed Patents:

US7619001 (Expiring Jun 20, 2020) covers Method for treating Multiple Sclerosis using pharmaceutical preparations with an excipient or at least one carrier using fumarates. The fumarates are limited to dimethyl fumarate (DMF), monomethyl fumarate (MMF), or their combination.

US8399514 (Expiring Feb 07, 2028) directed to methods of treating patients needing treatment for Multiple Sclerosis (MS). The heart of the treatment, and a requirement of every claim is administering about 480 milligrams (mg) per day of certain fumarates. Id. The fumarates are limited to dimethyl fumarate (DMF), monomethyl fumarate (MMF), or their combination.

US ‘514 has also been involved in the following proceedings before the Patent Trial and Appeal Board (“Board”):

• IPR2015-01993 by Coalition for Affordable Drugs V LLC (In favour of Biogen)
• IPR2015-01136 by Coalition for Affordable Drugs LLC (Terminated)
• IPR2018-01403 by Mylan Pharma Inc. (In favour of Biogen)
• IPR2019-00789 by Sawai Inc USA (Trial Instituted)

On Feb 05, 2020 PTAB has pronounced the judgement for US Patent No. 8,399,514 B2 against the generic drugmaker's Inter Partes Review (IPR2018-01403, Mylan Pharma Inc.) seeking to overturn the patent covering Tecfidera. The drug, which had $4.4 billion in sales last year, could remain protected through February 2028.

The IPR2018-01403 on US ‘514 was filed on the following ground on claims as:

Ground	Claim	Basis	References/Prior Art
01	1-20	§ 103(a)	Biogen Press Release & Schimrigk 2004
02	1-20	§ 103(a)	Kappos 2006 and Schimrigk 2004
03	1-20	§ 103(a)	Kappos 2006 and WO ’342
04	1-20	§ 103(a)	Kappos 2006, Clinical Trials ,Joshi ʼ9997, and ICH Guideline

Illustrative of the challenged claims:

Independent claims 1, 11, 15, and 20, reproduced below:

1. 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 mg per day.

11. A method of treating a subject in need of treatment for multiple sclerosis consisting essentially of orally administering to the subject about 480 mg per day of dimethyl fumarate, monomethyl fumarate, or a combination thereof.

15. A method of treating a subject in need of treatment for multiple sclerosis comprising orally administering to the subject pharmaceutical composition consisting essentially of

(a) a therapeutically effective amount of dimethyl fumarate and

(b) one or more pharmaceutically acceptable excipients, wherein the therapeutically effective amount of dimethyl fumarate is about 480 mg per day.

20. A method of treating a subject in need of treatment for multiple sclerosis comprising treating the subject in need thereof with a therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof, wherein the therapeutically effective amount of dimethyl fumarate, monomethyl fumarate, or a combination thereof is about 480 mg per day.

Argument by Mylan

Reference 1: Biogen Press Release & Schimrigk 2004

Mylan asserts that claims 1–20 are unpatentable under 35 U.S.C. § 103 as obvious over the combination of the Biogen Press Release and Schimrigk 2004. Pet. 34–44. Petitioner contends that the Biogen Press Release discloses that a Phase II study designed to evaluate the efficacy and safety of BG-1216 resulted in “a statistically significant reduction in the total number of gadolinium-enhancing brain lesions as measured by MRI.”

Mylan contends that, because it was known that DMF was effective in treating MS based on the teachings of Schimrigk 2004, skilled artisans would have been motivated to take the next obvious drug development step:

• optimize the dose of DMF, 
• taking into account its known side-effect profile, 
• patient compliance issues arising from three times daily dosing, and 
• general principles of drug development.

However, PTAB evaluate that the Biogen Press Release does not disclose an effective dosage of DMF. As for the dose of DMF used in the study, Mylan contends that a person of ordinary skill in the art would have understood that the Biogen Press Release reports the results of a study disclosed in Kappos 2005.

Biogen also as Patent Owner contends that Schimrigk 2004 does not teach that any range of DMF doses (e.g., from 360 to 720 mg/day) were effective to treat MS, “and certainly not 480 mg/day DMF monotherapy.”

PTAB also shown disagreement with persuasiveness over Petitioner’s rebuttal with testimony of experts Drs. Corboy, Benet, and McKeague supporting Petitioner’s contention that the “there is nothing unexpected about the magnitude of efficacy of 480 mg/day of DMF in treating MS.”

PTAB concluded with considered all the evidence, Mylan has not demonstrated by a preponderance of the evidence the unpatentability of claims 1–20 of the ’514 patent.
Potential market of DMF:
As per Biogen financial statement:


Europe prospective:

The family equivalent patent in Europe is also under opposition since 2014. Biogen is paying pay Denmark’s Forward Pharma $1.25 billion and potentially royalties in the US and EU, in order to protect patents on Tecfidera (dimethyl fumarate).

As a part of successive follow-up molecule BIIB098 (diroximel fumarate) VUMERITY as new drug 505(b)(2), designed to improve on the safety profile of Biogen’s established MS blockbuster Tecfidera (dimethyl fumarate), particularly with regard to its gastrointestinal tolerability has also been approved by FDA on Oct 2019 and having Q4 sales were just $5 million but an encouraging figure for Biogen.