In recent years, the Federal Circuit has reviewed a number of “second generation” patents that are directed toward new discoveries related to previously known, and often commercially viable, drugs. These inventions include new salt forms or stereoisomers, new diseases to be treated and improved drug formulations. Provided they represent improvements within fields of study that are frequently very crowded, these developments often result in patents that provide additional protection for drugs that are covered by soon-to-expire, “first generation” patents.

A tally of court of appeals cases in which these patents are scrutinized, however, shows many being held as invalid. In these decisions, the court regularly views these “discoveries” as obvious variations of what would have been known to one of skill in the art. See, e.g., Pfizer v. Apotex (2007), Aventis v. Lupin (2007), In re Kao (2011), and Tyco v. Mutual Pharma (2011). In spite of this trend, two recent court of appeals cases show that improvement patents are not automatically dismissed by the court as lacking obviousness.  

In Eli Lilly v. Actavis Elizabeth, the court of appeals upheld a claim specifying a method of treating attention-deficit/hyperactivity disorder (ADHD) using the previously known drug tomoxetine. Tomoxetine, marketed in the U.S. as the ADHD drug Strattera, had previously been studied for the treatment of urinary incontinence, and was a known norepinephrine inhibitor.

In response to the infringement suit, the defendants in this case argued that the method claim should be held as obvious, submitting that the inventors simply “substituted one potent selective norepinephrine reuptake inhibitor (tomoxetine) for another (desipramine) known to be effective in treating ADHD.” The court disagreed, noting significant side effects associated with desipramine, as well as a lack of teaching in the art to solely target norepinephrine reuptake inhibition to treat the claimed condition. The court also observed tomoxetine’s failure to treat depression “was contrary to the likelihood that tomoxetine would be effective to treat ADHD.”

The court of appeals similarly upheld a claim to a new pharmaceutical formulation of a known drug in Unigene Labs v. Apotex. In this case, the court upheld a district court’s grant of summary judgment of non-obviousness with respect to a formulation comprising salmon calcitonin and a specific concentration of citric acid, as well as other components. Salmon calcitonin is a known regulator of calcium in the blood, and is useful for the treatment of osteoporosis.

When filing a New Drug Application for this formulation (Fortical), Unigene demonstrated bioequivalence with Miacalcin, another formulation comprising salmon calcitonin. The Fortical and Miacalcin formulations use different components to act as both an absorption enhancer and a surfactant—Fortical relies on 20 mM citric acid for this function, while Miacalcin uses benzalkonium chloride (BZK).

Referring to the Miacalcin formulation as the “reference composition,” the court held that one of skill in the art would have had no motivation to replace BZK with 20 mM citric acid. In its review of certain secondary references, the court noted that one U.S. patent disclosed solid, not liquid, oral dosage forms, as well as concentrations of citric acid that were much higher than what was claimed. Another publication disclosed the use of citric acid in liquid nasal sprays, but as a “pH adjuster or buffer,” not a surfactant or preservative. The court also proposed that yet another U.S. patent taught away from the use of citric acid, as it disclosed a study in which citric acid yielded “discouraging” test results.

In view of this analysis, the court took the position that even if “there was a design need and market pressure to develop a pharmaceutical formulation that is bioequivalent to Miacalcin, there is no evidence in the record that [the] claim … would be an obvious solution to those motivations.” In fact, the court held that “the ‘about 20.0 mM citric acid’ limitation alone supports the district court’s grant of summary judgment of nonobviousness.”

Since the Supreme Court’s decision in KSR v. Teleflex (2007), the court of appeals has made some rulings that arguably fail to recognize the ingenuity and effort devoted to an improvement invention (see, especially, Bayer Schering Pharma AG v. Barr Laboratories (2009)).

However, like Eli Lilly v. Teva (2010), in which methods of treating osteoporosis using raloxifene were held to be non-obvious, and Abbott v. Sandoz (2008), in which a claim to a pharmaceutical formulation comprising the antibiotic clarithromycin was upheld, the Eli Lilly and Unigene cases instill confidence in the pharmaceutical patent practitioner that second-generation discoveries backed by sound scientific discovery and analysis can withstand an allegation of non-obviousness.