Federal Circuit Affirms Validity of Endo Pharmaceuticals Patent for Morphinan Pain Relief Compounds

The Federal Circuit held that where an asserted prior art reference incentivizes a certain objective but does not instruct as to how the objective should be obtained, it does not provide a motivation to combine in an obviousness analysis.

Federal CircuitThe Federal Circuit recently affirmed a district court ruling finding patent infringement after holding that Actavis LLC, Actavis South Atlantic LLC, and Teva Pharmaceuticals USA, Inc. (collectively, “Actavis”) failed to prove by clear and convincing evidence that the claims asserted by Endo Pharmaceuticals and Mallinckrodt LLC (collectively, “Endo”) were invalid. See Endo Pharms., Inc. v. Actavis LLC, No. 2018-1054, 2019 U.S. App. LEXIS 13348 (Fed. Cir. May 3, 2019) (Before Wallach, Clevenger, and Stoll J.) (Opinion for the Court, Wallach, J.) (Dissenting opinion, Stoll, J.). However, the decision was not a unanimous one, with Judge Stoll authoring a dissent that would have reversed the district court.

The patent at issue, U.S. Patent No 8,871,779 (the “‘779 patent”), is directed generally to compounds known as “morphinan alkaloids,” which are used for pain relief. More specifically, the ‘779 patent concerned processes for making “highly pure” morphinan products in the form of hydrochloride salts. Actavis claimed that the ‘779 patent was invalid, citing three key references as prior art. The first reference was a scientific article from 1957 by Ulrich Weiss (the “Weiss reference”) discussing a method for producing oxymorphone, a compound within the scope of the asserted claims. The second reference was U.S. Patent Application No. 2005/0222188 (the “Chapman reference”), which disclosed a purification process related to the asserted claims. Finally, the third reference was another article from 1967 by Henry Rapoport et al. (the “Rapoport reference”), which disclosed another purification process for oxycodone. The district court found that none of these references rendered the asserted claims obvious, and Actavis appealed.

Claim Construction

On appeal, Actavis first challenged the district court’s construction of the term “14-hydroxymorphinone,” a component relevant to the asserted claims. The district court relied on intrinsic evidence from the claim language to determine that 14-hydroxymorphinone referred to the salt form of the compound, “14-hydroxymorphinone hydrochloride,” and the Federal Circuit affirmed. The asserted claims claimed only 14-hydroxymorphinone as a part of the salt or hydrochloride form of the disclosed compounds, and not as a separate non-salt or non-hydrochloride component. Extrinsic evidence also supported this construction, as Actavis’s expert agreed that the disputed term would refer to the salt form of the compound. Therefore, as used in the claims, the Federal Circuit agreed that 14-hydroxymorphinone referred to the salt 14-hydroxymorphinone hydrochloride.


The Federal Circuit then turned to the district court’s obviousness determination, wherein the Court affirmed that Actavis had not proven the ‘779 patent was invalid as obvious by clear and convincing evidence. The district court found that a person of ordinary skill in the art would not have understood that it was feasible to combine the Weiss reference’s process and the Chapman reference’s process to yield the claimed compounds and purification levels. Specifically, the district court found that there would not be a reasonable expectation of success when combining the teachings of Chapman with the reaction taught in Weiss because Weiss disclosed a material difficulty that Chapman did not provide a viable solution for. The district court also found that the process of Rapaport would not ever be believed by a person of ordinary skill to yield some of the purity levels described in the ‘779 patent. The Federal Circuit found that the district court did not err in reaching these conclusions.

The Court also referenced the district court’s analysis of a relevant Food and Drug Administration (FDA) communication discussing the problems with impurities in oxymorphone and setting new approval guidelines for impurity levels. The district court found that this FDA reference introduced a mandated market force incentivizing purification, but it did not teach how the purification should be obtained and therefore could not serve as a motivation to combine in an obviousness analysis. Rather, the district court found that the FDA communication revealed that “the FDA recognized the challenge the mandate posted for companies,” and would not have been enough to overcome the disclosures of the Weiss, Chapman, and Rapaport references, which a person of ordinary skill in the art would not reasonably believe could lead to the targeted purity levels in the claimed compounds. Finally, the Court cited to the extensive experimentation undertaken by the inventors of the ‘779 patent to ultimately produce the compounds referenced in the asserted claims.

Judge Stoll Dissents

Actavis argued, and the majority dismissed, that the district court had imposed a heightened standard in its application of the reasonable expectation of success test. Judge Stoll, however, agreed with Actavis on this point in her dissent. Judge Stoll argued that the FDA regulatory requirement in and of itself disclosed every limitation of claim 1, even though the district court found that it did not disclose anything substantively relevant to obviousness.

She also argued that the district court erred by imposing a requirement that a reference must teach how to solve a problem to provide motivation to combine, which conflated the enablement and reasonable expectation of success requirements with motivation to combine. Finally, Judge Stoll felt that the district court applied an erroneously high standard for reasonable expectation of success by requiring a “definite solution” and proof of actual success, such as by requiring proof that the technique performed in the Rapaport reference was functionally and successfully used. She reiterated that the standard for obviousness requires only a reasonable expectation of success and not proof of actual success.

In conclusion, Judge Stoll noted that:

This is not a typical Hatch-Waxman case where the patentee provided the public with a new drug, formulation, or manufacturing process. While Mallinckrodt’s patent specification is directed to a specific process for achieving the FDA’s objective, Mallinckrodt did not claim that process. Mallinckrodt instead claimed the FDA mandate. The FDA sought to make oxymorphone safer for the public and Mallinckrodt took advantage by claiming the directive itself, securing exclusive rights to a drug first approved in 1959. This is not the type of innovation that the patent system and the obviousness standard were designed to protect.


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Join the Discussion

2 comments so far.

  • [Avatar for Anon]
    May 16, 2019 04:29 pm

    I still have not seen anyone (properly) distinguish the “TO COMBINE” portion of the phrase “motivation to combine” from a general (and generally wrong) sense of simple “motivation.”

    Motivation of anything in and of itself of that “anything” as a separate item is NOT a “motivation to combine.”

    Leastwise, not in the meaningful patent sense.

    Anything that has value has a motivation in and of itself for that value. The error in confusing the motivation OF value in a single item and broadening that to some sort of “of course, combining of something of value with anything is an improper application of the law of 35 USC 103. What this basically does is turn 103 into an “any-number-of-references” 102.

    This is almost the opposite problem of those that want some type of “synergy” in combinations in order to merit patentability. Combinations do not require synergy (not to say that having synergy is a ‘bad’ thing).

    But just as synergy is not an actual requirement, there IS a requirement for finding a motivation outside of the inherent singular worth of a reference to move from the mere word “motivation” to the proper legal phrase “motivation to combine.”

  • [Avatar for Daniel Hanson]
    Daniel Hanson
    May 16, 2019 12:11 pm

    This opinion clarifies a number of principles related to “reasonable expectation of success”:

    1. Practical concerns in the prior art, without solutions to those difficulties, ought not to be ignored or trivialized. Such concerns weigh against a reasonable expectation of success.
    2. Whether the prior art talks about “success” or not can depend upon what is recited in the claims at hand. Here, the prior art did not “state that any resulting compounds have the purity levels of those in the Asserted Claims.” And in fact, the prior art included some information that would suggest to a person of skill in the art that the purity levels recited in the claims in question would not be attained.
    3. An FDA mandated purity level may incentivize purification to the level recited in the claims, but that does not mean there was a reasonable expectation of success: “FDA communications recite a goal without teaching how the goal is attained.”
    4. Even if the FDA mandate represented motivation, it did not establish reasonable expectation of success, because reasonable expectation of success and motivation to combine are “two different legal concepts.” (In the Novartis case decided ten days later, the Federal Circuit discussed motivation to combine and reasonable expectation of success as severable issues.)
    5. Reasonable expectation of success may be further negated by evidence of experimentation, which in this case showed that genuine success was actually rather hard to come by.
    6. In the term “reasonable expectation of success,” the word “reasonable” means that the expectation of success need not be absolute. Of equal (if not greater) importance, however, is the word “expectation,” meaning that there must be some evidence that the approach is promising. The standard is not a “reasonable possibility of success,” nor a “reasonable hope of success.”