Takeaway: A reasonable expectation of success is not absolute predictability of success.

In its Decision, the Board determined that Petitioner had established a reasonable likelihood of prevailing in showing the unpatentability with respect to at least one IPR of claims 1-10 of the ’135 patent.

According to the Board, the ’135 patent relates to “methods of treating a subject suffering from a disorder associated with hyperlipidemia and/or hypercholesterolemia.” Petitioner challenges the patentability of claims 1–10 of the ’135 patent as obvious based on (1) Pink Sheet and Chang, and (2) Stein and Chang.

Patent Owner asserted that the Petition should be denied on the basis that Petitioner failed to name all of the real parties in interest. The Board stated that the “fact that the Coalition for Affordable Drugs may have named IP Navigation Group, LLC and nXn Partners, LLC as real parties in interest in other Petitions, but failed to name them as real parties in interest, is not sufficient, by itself, to demonstrate that Petitioner failed to name all the real parties in interest.”

Petitioner contended that the ’135 patent is not entitled to filing date of its provisional application, Provisional application No. 60/550,915. Petitioner alleged that the independent claims of the ’135 patent recite using an MTP inhibitor, salts thereof, or “the piperidine N-oxide thereof;” however, the ’915 provisional does not use the term, or presents by structure, a piperidine N-oxide. Patent Owner asserted that a person of ordinary skill would have been aware of piperidine N-oxide compound derivatives, and would have understood that the disclosure of the piperidine compounds in the provisional application includes piperidine N-oxides, a sub-class of piperidines. The Board stated that Patent Owner’s arguments do not explain why the ordinary artisan would realize that the invention relates to a piperidine N-oxide of the illustrated compound, lomitapide.

Petitioner argued that “the ’915 provisional focused on different dose-range combinations, and that the particular numerical ranges claimed (e.g., about 2–13 mg/day for the first dose) cannot be teased out of the multiplicity of dose ranges listed in the ’915 provisional, either expressly or inherently.” Patent Owner asserted that an ordinary artisan would have used a 70 kg person to calculate a range based on the disclosure in ¶ [0047] of the specification. The Board stated that “Patent Owner’s arguments do not explain why the ordinary artisan would realize, upon reading the ’915 provisional, that the invention relates to the three dosage ranges required by the challenged claims.”

Patent Owner argues that the art relied upon by Petitioner was before the Examiner during prosecution, even if they were submitted in a supplemental information disclosure statement that was filed after an allowance. The Board declined to exercise its discretion under 35 U.S.C. § 325(d) to deny the Petition.

With regard to Petitioner’s first obviousness challenge, Petitioner asserted that an ordinary artisan would have combined Chang with Pink Sheet because Chang teaches that lomitapide is one of three discussed MTP inhibitors, another of which is implitapide, the MTP inhibitor used by Pink Sheet, that are furthest along in clinical trials, with each working in humans and being similarly effective. According to Petitioner, Chang also noted the issues with side-effects associated with MTP inhibitors, and thus could not compete with statins as monotherapy and this problem was also addressed by Pink Sheet, which reports a solution to the problem.

Patent Owner argued that Pink Sheet merely reports on the Stein presentation, making the challenge based on Pink Sheet redundant on the ground based on Stein. The Board disagreed with Patent Owner in this regard. Patent Owner also argued that Pink Sheet 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. The Board stated that Patent Owner provided “no persuasive evidence on this record that the ordinary artisan would discount [the Pink Sheet’s] teaching just because it was in the context of a Phase II trial.” The Board also concluded that Petitioner has sufficiently demonstrated that Chang provides a reason to substitute lomitapide for implitapide as taught by Pink Sheet.

Patent Owner further contended that Chang in general teaches away from the use of MTP inhibitors. According to Patent Owner, the ordinary artisan would not have combined Pink Sheet with Chang given that “clinical development of lomitapide had been previously halted due to safety concerns.” The Board noted that Pink Sheet, which was published February 16, 2004, acknowledges that MTP inhibitors had been pursued by a number of companies, but that the toxicity seen was most likely related to the high doses used during trials. Thus, Pink Sheet was aware of the potential adverse effects associated with MTP inhibitors, but was still pursuing Phase II studies.

Patent Owner argued that the results of the study disclosed by Pink Sheet have not been reported in the prior art, and thus the “work could not have contributed to a reasonable expectation of success for lomitapide.” The Board stated that “all that is required is a reasonable expectation of success, not absolute predictability of success.” The Board stated that “Pink Sheet specifically acknowledges the toxicity seen in other studies, noting that was most likely due to high doses used, and thus an escalating dose would be used to determine a safe and tolerable dose.” In addition, “Chang notes that both implitapide and lomitapide have been the subject of clinical studies.” Thus, the Board determined that Petitioner has set forth a sufficient reasonable expectation of success of combining Pink Sheet with Chang to arrive at the method of challenged claim 1.

The Board concluded that Petitioner has shown a reasonable likelihood that independent claim 1 is rendered obvious by Pink Sheet and Chang. According to the Board, Patent Owner did not specifically address the patentability of dependent claims 2 and 5–8 over the combination of Pink Sheet and Chang. The Board was not persuaded by Patent Owner’s arguments regarding dependent claims 3 and 4. Thus, the Board concluded that Petitioner has shown a reasonable likelihood that dependent claims 1–8 are unpatentable as being rendered obvious by the combination of Pink Sheet and Chang.

With regard to claims 9 and 10, Patent Owner argued that, even if Pink Sheet could be read as teaching an escalating dose, it only discloses adjusting the amounts after five weeks, and does not disclose the intervals required by independent claims 9 and 10. The Board noted that Dr. Zusman stated, “ordinarily skilled artisans would have been familiar with side effects of lipid-lowering drugs and experienced with how to minimize them” and that “[t]his knowledge is reflected in the PDR teaching escalating dose titration regimens for common cholesterol-lowering drugs such as statins, fibrates and niacin, each and every one of which includes a 4 week period between adjusting dose levels, and many of which also include a 2 week period.” (emphasis original). Thus, the Board determined that Petitioner has reasonably demonstrated that the dosing schedules required by independent claims 9 and 10 would have been obvious to the ordinary artisan at the time of invention.

In regard to Petitioner’s obviousness challenge based on Stein and Chang, the Board determined that Petitioner had established that Stein was a printed publication and qualifies as prior art to the ’135 application. Petitioner relied upon Stein for the same teachings as Pink Sheet, and relied upon Chang for the same teachings as discussed above. Patent Owner merely incorporated the arguments made above. Because those arguments were not convincing, the Board concluded that Petitioner has shown a reasonable likelihood that claims 1–10 are rendered obvious by Stein and Chang.

COALITION FOR AFFORDABLE DRUGS VIII, LLC v. THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA, IPR2015-01835

Paper 7: Decision on Institution

Dated: March 7, 2016

Patent 8,618,135

Before: Michael P. Tierney, Lora M. Green, and Grace Karaffa Obermann

Written by: Green

Related Proceedings: IPR2015-01836