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Federal Circuit Affirms Summary Judgment of Nonobviousness of FORTICAL Formulation

By Aaron Barkoff

Unigene Labs and Upsher-Smith v. Apotex, No. 2010-1006 (Fed. Cir. 2011)

In a decision yesterday, the Federal Circuit affirmed a district court opinion granting Unigene's motion for summary judgment that claim 19 of U.S. Patent No. RE40,812 is not invalid for obviousness.  Claim 19 of the '812 patent covers the pharmaceutical formulation of FORTICAL (calcitonin nasal spray).  The Federal Circuit also affirmed the district court's denial of Apotex's motion to breach the attorney-client privilege under the crime-fraud exception and the district court's determination that Apotex had waived certain counterclaims, but the validity decision is the most interesting.

Claim 19 of the '812 patent recites:

A liquid pharmaceutical composition for nasal administration comprising about 2,200 MRC units of salmon calcitonin, about 20 mM citric acid, about 0.2% phenylethyl alcohol, about 0.5% benzyl alcohol, and about 0.1% polyoxyethylene(2) sorbitan monooleate.

Unigene filed its NDA for FORTICAL under section 505(b)(2), naming Novartis's MIACALCIN as the reference listed drug.  Whereas MIACALCIN contains benzalkonium chloride ("BZK"), an absorption enhancer, preservative and surfactant, FORTICAL contains citric acid (absorption enhancer), phenylethyl- and benzyl-alcohol (preservatives) and polysorbate 80 (surfactant).  Unigene also filed a patent application on its formulation, which issued as the '812 patent.

Apotex filed an ANDA for a generic version of FORTICAL, alleging that claim 19 of the '812 patent is invalid for obviousness.  Apotex argued that the formulation of claim 19 would have been obvious in light of MIACALCIN, a prior art patent (disclosing solid formulations of salmon calcitonin) and a prior art publication authored by Day.  The district court granted summary judgment of nonobviousness, which is relatively rare in Hatch-Waxman cases.

On appeal, the Federal Circuit began its obviousness analysis with an extensive discussion of KSR, in which the Supreme Court held that the teaching-suggestion-motivation (TSM) test is not a required part of the obviousness analysis.  The Federal Circuit acknowledges this, quoting from KSR:  "The obviousness analysis cannot be confined by a formalistic conception of the words, teachings, suggestion, and motivation . . . ."  But in the next paragraph, the Federal Circuit seems to rely on the TSM test, quoting from its 2006 decision in Eli Lilly v. Zenith Goldline:

to establish a prima facie case of obviousness based on a combination of elements in the prior art, the law requires a motivation to select the references and to combine them in the particular claimed manner to reach the claimed invention.

The Federal Circuit then explained how KSR should be applied in cases involving pharmaceutical formulation patents.  The court compared the obviousness analysis in pharmaceutical compound cases to that in pharmaceutical formulation cases:

A prima facie case of obviousness in the chemical arts is often based on a known compound, called a "lead compound," which serves as a starting point for a person of ordinary skll developing the claimed invention.  Where the patent at issue claims a chemical compound, a lead compound is often used to show structural similarities between the claimed compound and prior art.  In the context of a composition or formulation patent where the patented formulation was made to mimic a previously FDA-approved formulation, the functional and pharmaceutical properties of the "lead compound" can be more relevant than the actual chemical structure (though not always mutually exclusive).  Thus, the term "reference composition" is more appropriate than "lead compound" when considering obviousness for a chemical composition. . . .

Addressing Apotex's obviousness position specifically, the Federal Circuit stated:  "To a person of ordinary skill in the art, citric acid would not be an obvious substitute for BZK's functions as an absorption enhancer and as a surfactant because citric acid has a vague role in even the closest prior art."  The court further found that the prior art actually teaches away from using citrict acid "as an absorption enhancing agent or stabilizing agent in a liquid formulation with a salmon cacitonin active ingredient."

The court concluded:  "There is no genuine dispute of material fact that a person of ordinary skill attempting to make a liquid composition to deliver salmon calcitonin into a human body through nasal administration, would not have considered using about 20 mM citric acid with the narrowly claimed amounts of benzyl alcohol, phenylethyl alcohol, and polysorbate 80, because the formulation would not be expected to perform properly to meet the specificity of a pharmaceutical use."

Full post as published by Orange Book Blog: At the Intersection of Patent Law and FDA Law on August 26, 2011 (boomark / email).