The Flip Side of Reasonable Expectation of Success is Unpredictability

October 11, 2019 – Article

            The Federal Circuit in a precedential opinion in Osai Pharmaceuticals, LLC v Apotex et al (Fed. Cir., October 4, 2019) reversed the USPTO’s determination of obviousness in an IPR for patent claims directed to the treatment of non-small cell lung cancer (NSCLC). Just reading the background of the first three or four pages of the decision, it was already apparent that the Court was not going to be affirming the PTAB’s decision. Notably:

Cancer treatment is highly unpredictable. Even though the EGFR was identified in some cancers as a drug target, the in vitro (i.e., in a test tube) effectiveness of a drug in inhibiting the EGFR turned out to be a poor proxy for how effective that drug actually was in treating cancer in vivo (i.e., in the body). Numerous EGFR inhibitors that showed promising in vitro activity failed for a variety of reasons. These included poor pharmacokinetics due to poor absorption or rapid metabolism (or both), undesirable drug-drug interactions, drug toxicity due to drug binding onto healthy cells, drug toxicity due to binding onto other receptors, and metabolite toxicity. Some drug candidates were limited by one or more of these shortcomings, further underscoring the unpredictable nature of cancer treatment. . .

. . . A great majority of therapies for NSCLC failed in clinical trials. . .

. . .After years of study, the inventors of erlotinib discovered that it was an effective targeted therapy for NSCLC. They claimed their invention in the ’221 patent.

Osai Pharmaceutical’s U.S. patent no. 6,900,221 Claim 44 is:

44. A method for the treatment of NSCLC (non small cell lung cancer), pediatric malignancies, cervical and other tumors caused or promoted by human papilloma virus (HFV), Barrett's esophagus (pre-malignant syndrome), or neoplastic cutaneous diseases in a mammal comprising administering to said mammal a therapeutically effective amount of a pharmaceutical composition comprised of at least one of N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine, or pharmaceutically acceptable salts thereof in anhydrous or hydrate forms, and a carrier.

            The Court picked apart each of the references that had been relied upon in reaching the conclusion “that a person of ordinary skill “would have combined Gibbs or OSI 10-K with Schnur and had a reasonable expectation of success of achieving the invention of challenged claims 44 and 53.” The Court was not kind in its decision (emphasis added):

As an initial matter, in reaching its conclusion, the Board misinterpreted the asserted references to teach more than substantial evidence supports. When the references are properly read, the Board’s finding that the asserted references provide a reasonable expectation of success also is not supported by substantial evidence.

But the asserted references do not disclose any data or other information about erlotinib’s efficacy in treating NSCLC. The record does not contain any clinical (human) data or preclinical (animal) data. It does not even include in vitro (test tube) data regarding erlotinib’s effect on NSCLC. At the same time, it is undisputed that NSCLC treatment was highly unpredictable with an over 99.5% rate of failure for drugs entering Phase II clinical studies.

The lack of erlotinib-NSCLC efficacy data or other indication of success here is significant because of the highly unpredictable nature of treating NSCLC, which is illustrated by the over 99.5% failure rate of drugs entering Phase II. See J.A. 4131. Indeed, this failure rate includes only drug candidates that were promising enough to make it to Phase II trials, and does not even take into account all of the drug candidates that failed in the preclinical stage and in Phase I studies. Further, it is undisputed that a drug’s success in treating one type of cancer does not necessarily translate to success in treating a different type of cancer, which underscores the unpredictability in cancer treatment generally.

            Of course, unpredictability has long been a means to argue for non-obviousness. To the extent an art is unpredictable, as the chemical arts often are, KSR’s focus on these "identified, predictable solutions" may present a difficult hurdle because potential solutions are less likely to be genuinely predictable.” Eisai Co. v. Dr. Reddy’s Laboratories, Ltd. (Fed. Cir. 2008). Nor is it to say that every case that touches on cancer treatment would come out the same way but this case provides a road map of sorts to rebut a challenge of obviousness, whether it be in the USPTO or other tribunals.