PTAB

IPR2015-01993

Coalition for Affordable Drugs V LLC v. Biogen Idec Ma Inc

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1. Case Identification

2. Patent Overview

  • Title: Treatment for Multiple Sclerosis
  • Brief Description: The ’514 patent discloses methods for treating multiple sclerosis (MS) by orally administering a pharmaceutical composition containing a therapeutically effective amount of dimethyl fumarate (DMF), monomethyl fumarate (MMF), or a combination thereof, wherein the effective amount is about 480 mg per day.

3. Grounds for Unpatentability

Ground 1: Obviousness of Claims 1-6, 8-16, and 20 over Kappos, ClinicalTrials, Joshi, and ICH Guideline E4

  • Prior Art Relied Upon: Kappos 2006 (a 2006 journal abstract), ClinicalTrials NCT00168701 (a 2005 clinical trial protocol), Joshi (Patent 7,320,999), and ICH Guideline E4 (a 1994 regulatory guidance document).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that the combination of prior art taught all elements of the challenged claims. Independent claim 1 requires a method of treating MS by orally administering about 480 mg/day of DMF/MMF. Kappos disclosed a Phase II clinical trial showing that 720 mg/day of a drug called BG00012 was effective in treating MS patients. ClinicalTrials was the protocol for the Kappos study and identified the active ingredient in BG00012 as DMF. Joshi taught that DMF was effective for treating MS generally and could be administered orally in capsules with excipients. The key limitation, the specific dose of "about 480 mg per day," was not explicitly taught but was allegedly obvious to try. Dependent claims adding limitations such as administration as a capsule (claim 2), for at least 12 weeks (claim 8), or in two equal doses (claim 4) were also disclosed or suggested by the prior art combination.
    • Motivation to Combine: Petitioner contended that a person of ordinary skill in the art (POSITA) would have been motivated to optimize the dose of DMF for treating MS. Kappos demonstrated efficacy at 720 mg/day, but both ClinicalTrials and Joshi disclosed known side effects like gastrointestinal irritation. The ICH Guideline E4 taught that dose-ranging studies are a standard, integral part of drug development to identify an optimal dose that balances efficacy with safety and tolerability. Therefore, a POSITA would combine the teachings to conduct routine experiments to find a lower, effective dose with fewer side effects than the 720 mg/day dose from Kappos.
    • Expectation of Success: A POSITA would have had a reasonable expectation of success. The process of dose optimization for a known-effective compound is a routine, not inventive, step in pharmaceutical development. The ClinicalTrials protocol itself allowed for dose reduction (e.g., from three 240 mg capsules to two) for patients who could not tolerate the higher dose, which would result in a 480 mg/day dose. This demonstrated that a lower dose was a contemplated and predictable modification.

Ground 2: Obviousness of Claim 7 over Kappos, ClinicalTrials, Joshi, ICH Guideline E4, and Joshi 2002

  • Prior Art Relied Upon: The same references as Ground 1, with the addition of Joshi 2002 (Patent 6,436,992).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground specifically targeted claim 7, which claims the method of claim 1 but requires the active ingredient to be MMF. Petitioner argued that the primary Joshi patent taught that MMF is the active metabolite of DMF. The additional reference, Joshi 2002, explicitly taught using MMF to treat MS.
    • Motivation to Combine: The motivation was to substitute one known therapeutic agent (DMF) with its known active metabolite (MMF), which was also known to be effective for the same indication. This is a common and obvious strategy in drug development. Given that Joshi taught MMF and DMF had essentially the same therapeutic efficacy, a POSITA would have found it obvious to substitute MMF for DMF in the method established by the other references.

Ground 3: Obviousness of Claims 17-19 over Kappos, ClinicalTrials, Joshi, ICH Guideline E4, and Begleiter

  • Prior Art Relied Upon: The same references as Ground 1, with the addition of Begleiter (a 2004 journal article).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground addressed claims 17-19, which add the limitation that the "expression level of NQO1 in the subject is elevated" after administering the drug. Petitioner asserted this was not a new limitation but an inherent property of administering DMF. Begleiter taught that DMF is a known inducer of NQO1 expression.
    • Motivation to Combine: The argument was based on inherency, not a new motivation to combine. Petitioner asserted that performing the obvious method of treating MS with 480 mg/day of DMF as established in Ground 1 would necessarily and inherently result in elevated NQO1 levels. Because this effect was an inherent result of the obvious method, it could not lend patentability to the claims.

4. Key Claim Construction Positions

  • "Therapeutically effective amount": Petitioner argued this term should be construed according to its definition in the ’514 patent’s specification, meaning an amount that results in prevention, delay, or amelioration of symptoms of a neurological disorder.
  • "Consisting essentially of": Petitioner contended this transitional phrase limits the scope of the claimed pharmaceutical composition to the specified active ingredients (DMF/MMF) and any other ingredients that do not materially affect the basic and novel characteristics of the invention.

5. Arguments Regarding Discretionary Denial

  • Petitioner argued that discretionary denial under §325(d) would be inappropriate despite a previous petition (IPR2015-01136) it had filed against the same patent. The petition asserted that new grounds and prior art were being presented that were previously unavailable. Specifically, an Interference decision issued after the first petition was filed had changed the effective priority date of the ’514 patent. This change made the Kappos 2006 reference available as prior art under 35 U.S.C. §102(b) for the first time, fundamentally altering the invalidity analysis and justifying a new proceeding.

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-20 of the ’514 patent as unpatentable.