Follow-on Pharmaceutical Formulation Found Non-Obvious
Unigene Laboratories v. Apotex (decided 8/25/11)By: C. Hunter Baker
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What This Means to You
- New pharmaceutical formulations of previously known pharmaceutically active ingredients can be patentable.
- Consider including negative results in application to show invention was not obvious.
- Balance scope of claim with “unexpected result” in view of prior art.
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Overview
In Unigene Laboratories, Inc. et al. v. Apotex, Inc. et al., the US Court of Appeals for the Federal Circuit (Federal Circuit) found Unigene’s follow-on pharmaceutical formulation of salmon calcitonin patentable over an earlier bioequivalent formulation of the same active ingredient. The Federal Circuit’s finding that the new formulation was not obvious is largely based on the fact that there was no teaching or suggestion in the art to use citric acid as an absorption enhancer. Citric acid had been used in a prior art formulation of salmon calcitonin, but the prior art did not teach the use of citric acid as an absorption enhancer.
This decision raises the possibility of obtaining patent exclusivity for new formulations of previously known active ingredients.
Case Background
Since 1995, Novartis has marketed a nasal spray formulation of calcitonin under the tradename Miacalcin® for the treatment of post menopausal osteoporosis. Subsequently, Unigene developed its own formulation of calcitonin (Fortical®), which is an alternative to and bioequivalent of Novartis’s Miacalcin®. Unigene obtained U.S. Patent Reissue 40,812 covering its formulation, which includes salmon calcitonin, polysorbate 80, phenylethyl alcohol, benzyl alcohol, and citric acid. In 2006, Apotex filed an Abbreviated New Drug Application (ANDA) to market a generic version of Unigene’s Fortical®, and Unigene filed suit for patent infringement.
On cross-motions for summary judgment on obviousness, the district court found that the prior art does not teach using citric acid as both a stabilizer and absorption enhancer, and Apotex appealed.
Decision Analysis
In reaching its decision, the Federal Circuit reviewed several pieces of prior art including Novartis’s Miacalcin® formulation. In comparing the two formulations, the Federal Circuit focused on the absorption enhancer. Novartis’s formulation uses benzalkonium chloride (BZK) as the absorption enhancer, and Unigene’s uses citric acid. Even though several prior art patents describe formulations of calcitonin with citric acid, the Federal Circuit found the citric acid was used as an acid/buffer, not as an absorption enhancer.
One prior art patent did include citric acid in a list of approximately 50 examples of absorption enhancers. However, the Federal Circuit discounted this teaching because the absorption enhancers in that patent yielded “discouraging” results. Therefore, citric acid would have been found undesirable as an absorption enhancer, and one of skill in the art would not have expected Unigene’s claimed formulation to work without an absorption enhancer. Unigene’s formulation was found to be a non-obvious solution to the problem of finding an alternative, bioequivalent formulation to Novartis’s Miacalcin®.
Takeaways
The Federal Circuit post-KSR has come down both ways on the obviousness of new pharmaceutical formulations of previously known active ingredients. This decision emphasizes the importance of pursuing narrow claims to a commercial product even in view of close prior art. The unpredictable nature of the development of a pharmaceutical formulation combined with a “teaching away” in the art can provide the key to patentability in such cases.
