PTAB

IPR2015-00643

Mylan Pharmaceuticals Inc. v. Yeda Research and Development Co. Ltd.

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1. Case Identification

2. Patent Overview

  • Title: Low Frequency Glatiramer Acetate Therapy
  • Brief Description: The ’250 patent discloses methods for treating relapsing-remitting multiple sclerosis (RRMS). The core of the claimed method involves administering a therapeutically effective regimen of three subcutaneous injections of a 40 mg dose of glatiramer acetate (GA) over a seven-day period, with at least one day between each injection.

3. Grounds for Unpatentability

Ground 1: Anticipation of Claims 1-13 and 19-20 by Pinchasi

  • Prior Art Relied Upon: Pinchasi (International Publication No. WO 2007/081975).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Pinchasi expressly discloses every element of the challenged claims. Pinchasi teaches a method of treating RRMS by administering 40 mg of GA on an "every-other-day" basis. Petitioner contended that this every-other-day dosing schedule inherently meets the limitation of "three subcutaneous injections ... over a period of seven days" because such a schedule results in alternating three-injection and four-injection weeks. Citing its proposed claim construction, Petitioner asserted that the open-ended term "comprising" in the independent claims means the claims cover regimens with at least three injections and are not limited to only three injections. Therefore, Pinchasi’s disclosure of an every-other-day regimen falls squarely within the scope of the claims. Pinchasi also explicitly taught that this regimen was sufficient to alleviate symptoms and reduce the frequency of relapses in RRMS patients.
    • Key Aspects: The viability of this ground depends heavily on the construction of the term "comprising" as open-ended, which would allow an every-other-day dosing schedule to anticipate a claim reciting "three injections over a period of seven days."

Ground 2: Obviousness of Claims 1-20 over Pinchasi in view of the 1996 FDA SBOA

  • Prior Art Relied Upon: Pinchasi (WO 2007/081975) and the 1996 FDA SBOA (a 1996 FDA pharmacology review document for Copaxone).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that if the claims were narrowly construed to require exactly three injections per week, the regimen would have been obvious over Pinchasi combined with the 1996 FDA SBOA. Pinchasi established that a 40 mg dose of GA was safe and effective. The 1996 FDA SBOA provided pharmacokinetic data showing that GA has a half-life of approximately 80 hours.
    • Motivation to Combine: A POSITA would combine these references because the 1996 FDA SBOA explicitly questioned the necessity of daily injections for a drug with such a long half-life. The SBOA reviewer recommended evaluating less frequent, intermittent administration to reduce patient discomfort. This provided a strong and direct motivation to modify the dosing regimens known in the art, including Pinchasi's every-other-day schedule, to a less frequent and more convenient fixed schedule, such as exactly three times per week.
    • Expectation of Success: The long half-life disclosed in the SBOA, coupled with the proven safety and efficacy of the 40 mg GA dose from Pinchasi, would have given a POSITA a reasonable expectation that a three-times-weekly 40 mg regimen would be safe and effective, providing a therapeutic profile similar to daily dosing but with improved patient compliance and tolerability.

Ground 3: Obviousness of Claims 1-20 over Pinchasi in view of Flechter 2002A

  • Prior Art Relied Upon: Pinchasi (WO 2007/081975) and Flechter 2002A (a 2002 clinical study on GA).

  • Core Argument for this Ground:

    • Prior Art Mapping: Pinchasi taught the use of a 40 mg GA dose, while Flechter 2002A disclosed that an alternate-day 20 mg GA regimen had similar efficacy to a daily regimen and that daily injections were therefore "unnecessary." Flechter 2002A also noted that alternate-day dosing resulted in higher patient compliance.
    • Motivation to Combine: A POSITA would combine these teachings to optimize GA therapy. Flechter 2002A's demonstration that less-than-daily dosing was effective and preferred by patients provided a clear motivation to apply this principle to the more potent 40 mg dose disclosed by Pinchasi. The goal would be to achieve the benefits of the higher dose while simultaneously improving patient compliance and convenience by reducing injection frequency to a fixed, predictable schedule like three times per week.
    • Expectation of Success: Given that Flechter 2002A established the viability of less frequent dosing and Pinchasi established the safety of the 40 mg dose, a POSITA would have had a high expectation of success in developing a safe, effective, and well-tolerated three-times-weekly 40 mg regimen.

  • Additional Grounds: Petitioner asserted an additional obviousness challenge against claims 1-20 based solely on Pinchasi, arguing that even if not anticipating, it would have been obvious for a POSITA to modify Pinchasi's every-other-day regimen to a fixed three-times-weekly schedule to improve patient convenience and adherence.

4. Key Claim Construction Positions

  • "comprising": Petitioner argued that the independent claims use the open-ended transitional phrase "comprising." Therefore, the claims should be construed to be inclusive and not exclude additional, unrecited steps. Specifically, a method of "comprising" three injections is not limited to only three injections but includes any method having at least three injections. This construction is critical to Petitioner's anticipation argument, as it allows Pinchasi’s every-other-day regimen (which alternates between 3 and 4 injections per week) to read on the claims.
  • "a therapeutically effective regimen": Petitioner contended that this term should be interpreted broadly as "a systemic plan of treatment." Petitioner argued that the use of this term, coupled with the indefinite article "a," does not limit the open-ended nature of "comprising" or otherwise close the claims to exclude additional injections.

5. Relief Requested

  • Petitioner requests institution of an inter partes review and cancellation of claims 1-20 of Patent 8,232,250 as unpatentable under 35 U.S.C. §§ 102 and 103.