Kyle Bass Claims Pink Sheet Article As Prior Art In Juxtapid Patent Challenge

University of Pennsylvania argues neither 2004 article nor slide presentation it describes constitutes prior art that would invalidate method of use claims.

Hedge fund investor Kyle Bass is relying on an article from "The Pink Sheet" in his efforts to invalidate two patents covering Aegerion Pharmaceuticals Inc.’s LDL cholesterol-lowering drug Juxtapid (lomitapide).

Bass’ group, the Coalition for Affordable Drugs, filed two inter partes review (IPR) petitions against the trustees of the University of Pennsylvania, the owner of the patents. The university licensed exclusive worldwide rights to lomitapide to Aegerion for the treatment of homozygous familial hypercholesterolemia (HoFH) and certain other therapeutic areas.

The petitions were submitted to the Patent and Trademark Office’s Patent Trial and Appeal Board (PTAB). Under the IPR administrative proceeding, the board considers whether to institute review of challenged patent claims and if it decides to do so must issue a final written decision within 12 months. Bass has targeted the pharmaceutical industry, filing more than 30 petitions against 12 companies in the past year (Also see "New Patent Battleground: Inter Partes Reviews Besiege Innovators" - In Vivo, 14 Dec, 2015.).

The petitions against the University of Pennsylvania focus on patents No. 8,618,135 and No. 7,932,268, which claim a method of treating high levels of fats (hyperlipidemia) and cholesterol (hypercholesterolemia) in the blood through a step-wise administration of increasing doses of lomitapide, a microsomal triglyceride transfer protein (MTP) inhibitor.

Bass, founder of Hayman Capital Management, contends that the patent claims are invalid as they “merely claim methods of using a known drug, to treat known medical conditions, for which the drug was known to be effective, with known dose-titration methods disclosed in the prior art.”

He cites as prior art a Feb. 5, 2004, presentation by Dr. Evan Stein discussing PPD Inc.’s plans for its MTP inhibitor implitapide and a Feb. 16, 2004, Pink Sheet article reporting on the presentation.

Slide Presentation And Pink Sheet Article Are Not Prior Art, U Penn Argues

The Pink Sheet article noted that PPD was adopting Merck & Co. Inc./Schering-Plough Corp.’s Zetia (ezetimibe) model in developing implitapide as an add-on therapy in the lipid-lowering market. The article briefly described PPD’s Phase II studies with dose titration occurring every five weeks based on safety and tolerability examined at four weeks. It said the starting doses were to be 10 mg daily, escalating by 5 mg/day every five weeks to a maximum 40 mg/day.

In the IPR petition challenging the ‘135 patent, Bass says the 2004 article taught an efficacy range that MTP inhibitors could safely target and market as adjunct therapy based on Zetia’s success in reducing low-density lipoprotein cholesterol over statin therapy alone. The petition says the Pink Sheet would have been reviewed and considered by persons of ordinary skill in the art.

For a skilled artisan reading the Pink Sheet article, “it would have been obvious to: identify other MTP inhibitors that performed at least comparably to implitapide in the clinic; use them in the escalating dosing regimen; and reasonably expect them to again work comparably to implitapide,” the petition states.

In a Dec. 8 preliminary response, the university contends that neither the Stein presentation nor the Pink Sheet article are prior art.

The university says Stein’s slide presentation is not a printed publication and thus does not qualify as prior art. It also notes that to qualify as a printed publication a reference must have been sufficiently accessible to the public interested in the art. In this case, the university says each of the more than 40 slides in Stein’s presentation would have been displayed for a maximum of 30 seconds. Further, the university says there is no evidence to establish who the target audience would have been or whether the attendees “possessed ordinary skill in the art” of the patent.

As for the Pink Sheet article, the university says the piece “can hardly be said to have ‘captured’ the complicated data” in the slide presentation.

It is “a single-page article relating to PPD’s attempt to develop implitapide as an add-on to statin therapy,” the response states. “It does not disclose a method of step-wise administration of increasing doses of implitapide for the treatment of patients, nor does it suggest that such a regimen could alleviate the known adverse events associated with high dosages of MTP inhibitors.”

Step-Wise v. Fixed Dose Administration

FDA approved Juxtapid in December 2012 as an adjunct to a low-fat diet and other lipid-lowering therapies for the treatment of adult patients with HoFH, a rare condition that causes premature and progressive atherosclerosis (Also see "Aegerion’s Juxtapid Needs Long-term Post-Market Cohort Study After FDA Nod" - Pink Sheet, 28 Dec, 2012.).

Bristol-Myers Squibb Co. initially sought to develop lomitapide for hyperlipidemia and hypercholesterolemia. The University of Pennsylvania says the company discontinued development when clinical trials with fixed doses of the drug revealed liver and gastrointestinal adverse effects. Bristol subsequently donated rights to the drug to the university. Daniel Rader, a professor at the university who invented the ‘135 and ‘268 patents, pursued a different approach to development of the drug.

In its preliminary response, the university says that while Bristol had attempted to develop a fixed dose of the drug, Rader sought to reduce the side effects by starting with a low dose of the drug and using a step-wise administration of increasing doses.

The ‘135 patent issued on Dec. 31, 2013, and the ‘268 patent issued on April 26, 2011.