PTAB

IPR2015-01835

Coalition for Affordable Drugs VIII LLC 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 ’135 patent describes methods for treating hyperlipidemia and hypercholesterolemia by administering a microsomal triglyceride transfer protein (MTP) inhibitor, specifically lomitapide, using a step-wise escalating dosing regimen. The claimed method is intended to reduce adverse side effects commonly associated with MTP inhibitors.

3. Grounds for Unpatentability

Ground 1: Obviousness over Pink Sheet in view of Chang - Claims 1-10 are obvious over Pink Sheet 2004 in view of Chang.

  • Prior Art Relied Upon: Pink Sheet (a February 16, 2004 article describing a presentation by Dr. Evan Stein) and Chang (a 2002 journal article on MTP inhibitors).
  • Core Argument for this Ground:
    • Prior Art Mapping: Petitioner argued that Pink Sheet expressly taught a method of treating hypercholesterolemia using a step-wise escalating dosing regimen for the MTP inhibitor implitapide to manage its therapeutic index. This regimen included a starting dose of 10 mg/day, escalating by 5 mg/day every five weeks, which falls within the ranges of challenged independent claim 1. Petitioner asserted that Chang, in turn, identified lomitapide (the claimed MTP inhibitor) as a member of the same drug class as implitapide and disclosed that both had "similar efficacy" in clinical studies. The combination of Pink Sheet's specific dosing method with Chang's disclosure of lomitapide as a known and similarly effective alternative allegedly rendered all claim elements obvious.
    • Motivation to Combine: Petitioner contended that Chang identified a known problem in the art: the significant adverse side effects of MTP inhibitors that hindered their commercial viability as a monotherapy. Pink Sheet disclosed a clear solution to this problem for implitapide: using a lower-dose, step-wise escalating regimen for adjunct therapy. A person of ordinary skill in the art (POSITA), aware of this problem and proposed solution, would combine these teachings. They would be motivated to apply the successful dosing strategy from Pink Sheet to other known MTP inhibitors with similar efficacy, like lomitapide as identified by Chang, to achieve the same benefits of reduced side effects.
    • Expectation of Success: Given that Chang taught lomitapide and implitapide were MTP inhibitors with similar mechanisms of action and comparable efficacy, a POSITA would have had a reasonable expectation of success. It was expected that substituting lomitapide for implitapide in the dosing regimen taught by Pink Sheet would predictably result in a similarly effective treatment for hypercholesterolemia with a manageable side-effect profile.

Ground 2: Obviousness over Stein in view of Chang - Claims 1-10 are obvious over Stein 2004 in view of Chang.

  • Prior Art Relied Upon: Stein (a February 5, 2004 presentation and slide deck) and Chang (a 2002 journal article on MTP inhibitors).
  • Core Argument for this Ground:
    • Prior Art Mapping: This ground is substantially similar to Ground 1, as the Pink Sheet article was a report on the Stein presentation. Petitioner argued that Stein is the primary source document and provided even more detail. Stein explicitly disclosed the "Phase I, Multiple-Day Dose Escalation Study of Implitapide" and outlined the proposed development plan, including a dose titration schedule starting at 10 mg daily with escalation by 5 mg every 5 weeks. This directly taught the core method of the challenged claims. As in Ground 1, Chang supplied the disclosure of lomitapide as a known and analogous MTP inhibitor.
    • Motivation to Combine: The motivation is identical to that in Ground 1, but strengthened by the greater detail in Stein. Stein provided extensive rationale for the adjunctive therapy approach, the commercial opportunity, and the clinical need for moderately effective (15-20%) LDL-C lowering agents, motivating a POSITA to apply this promising strategy to other known MTP inhibitors like lomitapide.
    • Expectation of Success: The expectation of success was the same as in Ground 1. A POSITA would reasonably expect that lomitapide, a known MTP inhibitor with similar properties to implitapide, would perform predictably when administered according to the specific, detailed dose-escalation protocol laid out by Stein.

4. Key Claim Construction Positions

  • “piperidine N-oxide thereof”: Petitioner argued this term is undefined by structure or chemical name within the ’135 patent’s specification. A general chemical understanding would involve adding an oxygen atom to the nitrogen atom of the piperidine ring in lomitapide, but the lack of specific disclosure was asserted to be a key deficiency.
  • “A subject suffering hyperlipidemia or hypercholesterolemia”: Petitioner proposed this includes humans and non-human mammals, such as rabbits used in clinical studies.
  • “effective amount”: This was construed to include any drug amount that improves a disease marker or inhibits MTP activity, even by as little as 10%.
  • “about”: This term was construed to mean approximately.

5. Key Technical Contentions (Beyond Claim Construction)

  • Improper Priority Claim: A central contention of the petition was that the ’135 patent was not entitled to the March 5, 2004 filing date of its provisional application (’915 provisional). Petitioner argued the provisional failed to provide adequate written description for key limitations of the issued claims. Specifically, it was argued that the provisional did not disclose the specific numerical dose ranges recited in the claims (e.g., a first dose of "about 2 to about 13 mg/day") and provided no support whatsoever for the "piperidine N-oxide thereof" limitation. Therefore, Petitioner argued the patent’s effective priority date is March 7, 2005, making the Pink Sheet and Stein 2004 publications prior art under 35 U.S.C. §102.

6. Relief Requested

  • Petitioner requested institution of an inter partes review and cancellation of claims 1-10 of Patent 8,618,135 as unpatentable under 35 U.S.C. §103.