The USPTO Patent Trial and Appeal Board (PTAB) decided to institute inter partes review (IPR) proceedings filed by Kyle Bass against two of the five Juxtapid patents listed in the Orange Book. Two of the cited references may qualify as § 102(b) prior art because the provisional application was found not to support certain aspects of the claims.

The Juxtapid® Patents At Issue

The patents at issue were U.S. Patent Nos. 7,932,268 and 8,618,135, licensed by Aegerion from the Trustees of the University of Pennsylvania. Juxtapid® is an oral capsule containing the active ingredient lomitapide mesylate for treating high cholesterol. Both the ‘135 patent and the’268 patent claim methods of administering at least three step-wise increasing doses of lomitapide mesylate. Claim 1 of the ‘135 patent is representative and recites:

1. A method of treating a subject suffering from hyperlipidemia or hypercholesterolemia, the method comprising administering to the subject an effective amount of an MTP inhibitor, wherein said administration comprises at least three step-wise, increasing dose levels of the MTP inhibitor wherein a first dose level is from about 2 to about 13 mg/day, a second dose level is from about 5 to about 30 mg/day, and a third dose level is from about 10 to about 50 mg/day,
and wherein the MTP inhibitor is represented by:

or a pharmaceutically acceptable salt thereof or the piperidine N-oxide thereof,
wherein each dose level is administered to the subject for about 1 to about 5 weeks.

Claim 1 of the ‘268 patent is nearly identical but recites that each dose level is administered to the subject for about 1 to 4 weeks.

Challenging The Priority Date

The Petitioner contended that the challenged claims were not entitled to the March 5, 2004 priority date of Provisional Application No. 60/550,915, asserting that the provisional application did not support the claimed piperidine N-oxide derivatives or the claimed dose ranges.

With regard to “piperidine N-oxide derivatives,” Petitioner argued that the closest disclsoure in the provisional application was the statement “[i]n some embodiments the MTP inhibitors are piperidine, pyrrolidine or azetidine compounds,” but that did not disclose piperidine N-oxides. The Patent Owner argued that a person of ordinary skill in the art would have understood “piperidine …. compounds” to include piperidine N-oxides. The PTAB sided with Petitioner, noting that “Patent Owner’s arguments … do not explain why the ordinary artisan would realize, upon reading the provisional application, that the invention relates to a piperidine N-oxide of the illustrated compound, lomitapide.”

With regard to the claimed dose ranges, Petitioner argued that the provisional application focused on different dose ranges. Patent Owner argued support as follows:

For example, the first claimed dosage level “from about 2 to about 13 mg/day,” is supported by Paragraph 0047 of the provisional application, which discloses that “[i]n some embodiments, the first dose level is from about 0.02 to about 0.59 mg/kg/day. In some embodiments, [the] second dose level is from about 0.06 to about 0.19 mg/kg/day.” Ex. 1006 at 14. The skilled artisan would see that exemplary embodiments reference a 70 kg person, and would use this weight to calculate a range between 1.4 mg/day to 13.3 mg/day, which supports “about 2 to about 13 mg/day.” Id. at 23.

The PTAB was not convinced by the Patent Owner’s arguments. For example, the PTAB explained:

When we look at the second two calculations for the second two dose levels, the claimed ranges are even more difficult to discern. Thus, again assuming a 70 kg man, a range of 4.2 mg per day to 41.3 mg per day is calculated for the second dose level, whereas the claims require a dose level from about 5 to about 30 mg/day. …. Finally, making the same assumption as to the patient being treated, a range of 14 mg per day to 41.3 mg per day is calculated for the third dose level, whereas the claims require a dose level from about 10 to about 50 mg/day.

Thus, the patents were accorded the March 7, 2005 filing date of the PCT application from which they both claim priority.

The Grounds of Institution

Because the challenged claims were not entitled to the March 7, 2004 priority date, two of the references cited by Petitioner may qualify as prior art under 35 U.S.C. §102(b):

  • Bayer/PPD Implitapide Development Follows Zetia Model As Statin Add-On, 66 THE PINK SHEET 17 (Feb. 16, 2004) (“Pink Sheet”)
  • Evan Stein, Microsomal Triglygeride [sic] Transfer Protein (MTP) Inhibitor (implitapide) program (Feb. 5, 2004) (“Stein”)

Patent Owner challenges whether the February 5, 2004 Stein webinar qualifies as a printed publication. If not, Petitioner contends that the slides qualify as prior art at least as of April 15, 2004, when they were available for download. If the Patent Owner attempts to antedate Stein, the PTAB will have to decided this issue.

The PTAB instituted IPR proceedings on the following grounds:

  • Claims 1-8 of the ‘268 patent and claims 1-10 of the ‘135 patent would have been obvious over Pink Sheet and George Chang et al., “Microsomal triglyceride transfer protein (MTP) inhibitors: Discovery of clinically active inhibitors using high-throughput screening and parallel synthesis paradigms,” Curr. Op. Drug Discovery & Devel. 5: 562 (2002) (“Chang”).
  • Claims 1-8 of the ‘268 patent and claims 1-10 of the ‘135 patent would have been obvious over Stein and Chang.

Grasping at Section 325(d)

In its Patent Owner Preliminary Response to the IPR Petition filed against the ‘135 patent, the Patent Owner urged the PTAB to exercise discretion under 35 USC 325(d) and deny the Petition because the asserted references were considered by the Examiner during the prosecution. The PTAB declined under “the facts and circumstances of the instant proceeding.” Indeed, the references were submitted in a supplemental Information Disclosure Statement filed after allowance, and not discussed during examination.

The PTAB has until March 7, 2017 to render its final decisions.

Other Juxtapid® Patents

The challenged patents include two of the latest-expiring Orange Book-listed Juxtapid® patent.

Proprietary Name Patent No Patent
Drug Substance Claim and Drug Product Claim Applicant
JUXTAPID 5712279 Feb 21, 2020 Yes AEGERION
JUXTAPID 6492365 Dec 10, 2019 No AEGERION
JUXTAPID 7932268 Aug 19, 2027 No AEGERION
JUXTAPID 8618135 Mar 7, 2025 No AEGERION
JUXTAPID 9265758 Mar 7, 2025 No AEGERION

U.S. Patent 9,265,758, which has the same March 7, 2025 expiration date as the ‘135 patent, just granted on February 23, 2016, with similar method claims. It will be interesting to see whether Kyle Bass challenges that patent as well.