PTAB

IPR2015-01836

Coalition for Affordable Drugs VIII v. Trustees Of University Of Pennsylvania

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Key Events
Petition
petition

1. Case Identification

2. Patent Overview

  • Title: Methods For Treating Disorders Or Diseases Associated With Hyperlipidemia And Hypercholesterolemia While Minimizing Side Effects
  • Brief Description: The ’268 patent discloses methods for treating hyperlipidemia and hypercholesterolemia by administering the microsomal triglyceride transfer protein (MTP) inhibitor lomitapide using a step-wise, escalating dosing regimen to minimize adverse side effects.

3. Grounds for Unpatentability

Ground 1: Claims 1-8 are obvious over Pink Sheet 2004 in view of Chang.

  • Prior Art Relied Upon: Pink Sheet 2004 (a February 16, 2004 article titled “Bayer/PPD Implitapide Development Follows Zetia Model As Statin Add-On”) and Chang (a 2002 journal article on MTP inhibitors).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Pink Sheet 2004 taught every element of the claimed method except for the specific use of lomitapide. It disclosed a step-wise escalating dosing regimen (starting at 10 mg/day, increasing by 5 mg/day every five weeks) for implitapide, another MTP inhibitor, to treat the same conditions (hypercholesterolemia) as an adjunct therapy. The disclosed dose levels and timing (safety evaluation at four weeks) fall within the ranges of the ’268 patent’s claims. Chang, a review of MTP inhibitors, taught that lomitapide belonged to the same class of drugs as implitapide and had demonstrated "similar efficacy" in clinical trials for lowering cholesterol.
    • Motivation to Combine: A POSITA, aware of the side-effect problems with MTP inhibitors as noted in Chang, would be motivated to apply the specific solution disclosed in Pink Sheet 2004—a step-wise escalating dosing regimen designed to improve safety and tolerability—to other known MTP inhibitors. Since Chang identified lomitapide as a prominent MTP inhibitor with similar efficacy to implitapide, a POSITA would combine the teachings to apply the dosing regimen to lomitapide to achieve the same benefits of improved efficacy and reduced side effects. The motivation was to apply a known problem-solving technique to a known, similar compound.
    • Expectation of Success: A POSITA would have a reasonable expectation of success in substituting lomitapide for implitapide in the dosing regimen. The references established that both were MTP inhibitors with similar mechanisms of action and comparable efficacy. The substitution was a simple case of applying a known technique to a different member of the same small, well-defined class of drugs, which is a predictable art.

Ground 2: Claims 1-8 are obvious over Stein 2004 in view of Chang.

  • Prior Art Relied Upon: Stein 2004 (a February 5, 2004 presentation by Dr. Evan Stein) and Chang.
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner asserted that the Stein 2004 presentation, which was the source for the Pink Sheet 2004 article, provided an even more detailed disclosure of the escalating dosing regimen for implitapide. It presented clinical trial data and a development plan showing a dose titration schedule (starting at 10 mg daily, escalating by 5 mg every 5 weeks after safety checks at 4 weeks) to achieve a targeted 18-24% LDL-C reduction. As in Ground 1, Chang supplied the teaching that lomitapide was a known MTP inhibitor with similar efficacy to implitapide.
    • Motivation to Combine: The motivation is largely the same as in Ground 1, but Petitioner argued it was strengthened by the detailed clinical data and marketing rationale in Stein 2004. Stein 2004 presented a clear strategy for making MTP inhibitors commercially viable as adjunct therapies by using lower, escalating doses to manage side effects. A POSITA would be motivated to apply this promising strategy to other well-known MTP inhibitors like lomitapide, which Chang identified as a leading candidate.
    • Expectation of Success: The expectation of success was identical to that in Ground 1. Petitioner contended that the additional clinical data for implitapide presented in Stein 2004 would further bolster a POSITA’s confidence that the same dosing strategy would be successful with lomitapide, a structurally and functionally similar compound.

4. Key Claim Construction Positions

  • “piperidine N-oxide thereof”: Petitioner argued this term is undefined by structure or chemical name in the specification. A POSITA would understand it to require adding an oxygen atom to the nitrogen of the piperidine ring in lomitapide, but the specification provides no support for this specific derivative or its clinical activity.
  • “about 1 to 4 weeks”: Petitioner argued that the prior art’s teaching of evaluating safety at four weeks and escalating the dose at five weeks is encompassed by the term “about four weeks.” It asserted this was an obvious and routine variation in clinical trial design, not a patentable distinction.

5. Key Technical Contentions (Beyond Claim Construction)

  • Denial of Priority Date: Petitioner dedicated a significant portion of its argument to contending the ’268 patent was not entitled to the filing date of its provisional application (March 5, 2004). The argument was that the provisional failed to provide written description support for the specific numerical dose ranges and the "piperidine N-oxide" limitation recited in the issued claims. Therefore, the patent’s effective priority date is its actual filing date of March 7, 2005, making Pink Sheet 2004 and Stein 2004 (both from February 2004) prior art under 35 U.S.C. §102(b).

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-8 of the ’268 patent as unpatentable under 35 U.S.C. §103.