Unigene Labs. and Upsher-Smith Labs v. Apotex (Fed. Cir. 2011)
One critical reading of this case is that the Federal Circuit intends to continue to take steps to ensure that important chemical formulation patents are considered valid. In particular, the court explicitly aligns the obviousness analysis of claims for formulations of known compounds with that of claims for novel compounds. In doing so, the court seemingly ignores KSR’s negative outlook on combination claims. The case is also important in the way that the (unclaimed) purpose of a particular element of a combination claim can be used to overcome an obviousness argument.
Background: Unigene's reissued patent No. RE40,812 covers its Fortical calcitonin nasal spray. Unigene developed Fortical as a bioequivalent alternative to Novartis's Miacalcin calcitonin nasal spray. Unigene relied on bioequivalence to the already approved formulation to speed its FDA approval process. The differences between the formulations are in the levels of non-pharmaceutically active components of the nasal spray.
In particular, the prior-art Miacalcin spray includes 2,200 I.U./mL of calcitonin and also sodium chloride, nitrogen, HCL, water, and benzalkonium chloride. Unigene’s Fortical contains the same amount of calcitonin, along with 20 mM citric acid, polysorbate 80, phenylethyl alcohol and benzyl alcohol. These contents in their required ratios are claimed in Unigene's patent.
In 2006, generic manufacturer Apotex filed an abbreviated new drug agreement (ANDA) to begin importing a generic version of Unigene's Fortical nasal spray before the patent's expected expiration date. Because that filing constitutes prima facie patent infringement under 35 U.S.C. § 271(e)(2), Unigene sued for infringement.
On summary judgment, the district court dismissed Apotex’s obviousness defense — holding that, as a matter of law, the asserted claims would not have been obvious at the time of invention. 35 U.S.C. 103(a).
On appeal, the Federal Circuit affirmed and provided a further analysis of how the Supreme Court’s KSR decision applies (or does not apply) in the chemical arts.
Begin with a “lead compound” or “reference composition”: In most chemical-compound cases, the obviousness analysis begins with the closest prior art compound — termed a “lead compound.” In this type of composition claim, an ordinary approach is to begin with a “reference composition.” Here, that reference is the Miacalcin formulation. Here, there was a strong market demand to identify a bioequivalent composition that avoids the Miacalcin patent since a bioequivalent would have the best chance of receiving FDA approval.
Although the prior art would point one of ordinary skill in the art toward a particular starting point and provide motivation to develop a bioequivalent, these factors to not indicate which bioequivalent among an infinite number of possible formulations is the best.
Here, Unigen focused on its use of 20 mM of citric acid as a absorption enhancer and surfactant in Fortical. The prior art Miacalcin uses BZK for that function. A prior art reference showed experimental data that citric acid mixed with calcitonin in tablet form increased absorption. However, the court ruled that reference “would not cause a person of ordinary skill to replace BZK in Miacalcin with 20 mM of citric acid in the normal course of research and development[, and therefore citric acid] would not be an obvious substitute for BZK’s functions.”
Unclaimed Function, Critical Importance: In making its decision, the court makes an important leap that is critical for its decision — namely that the role or function of citric acid in the claimed invention is as an absorption enhancer and surfactant. The claims do not require that functionality. However, the court determined that the citric acid actually serves as a substitute for BZK and therefore its addition will only be obvious if it would have been obvious as a substitute for BZK.
Once framed as a question of substitution, the court then looked to the prior art and found that the role of citric acid in the prior art was only vaguely known and therefore could support a decision that it would have been obvious to substitute citric acid for the BZK functionality. A separate prior art reference used citric acid in a nasal compound (like Fortical), but included a statement that the citric acid was “not used as an absorption enhancing agent” but instead only as a buffer. That reference also suggests that citric acid would not be an acceptable absorption agent.
In addition, the prior art used different concentration levels of citric acid and only non-human mammalian tests — factors that tend to disrupt any obviousness argument.
Summary Judgment of Nonobviousness Affirmed.
Notes from around the patently-o-sphere:
Kevin Noonan writes that “the decision provides a contrast between how the Court views chemical obviousness for pharmaceutical formulations today, and the views contained in the Court's opinion in Pfizer, Inc. v. Apotex, Inc.”
Aaron Barkoff notes that the opinion aligns the obviousness analysis for formulation claims (for known compounds) with that of claims for novel compounds.
Ryan Alley writes that “I get the feeling the case is pushing the boundaries of nonobviousness a little too far.”
Patent Hawk writes that in this case, the “CAFC set its own formula for chemical obviousness”