IP Law Daily Court holds Amneal’s generic nasal spray does not infringe Merck patent for Nasonex
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Tuesday, January 31, 2017

Court holds Amneal’s generic nasal spray does not infringe Merck patent for Nasonex

Merck Sharp & Dohme Corp. did not prove by a preponderance of the evidence that Amneal Pharmaceuticals LLC’s generic mometasone furoate nasal spray infringed on Merck’s patent related to the nasal spray Nasonex, the federal district court in Wilmington, Delaware has held (Merck Sharp & Dohme Corp. v. Amneal Pharmaceuticals LLC, January 30, 2017, Robinson, S.).

The ‘353 Patent. Merck owns U.S. Patent No. 6,127,353 ("the ‘353 Patent"), titled "Mometasone furoate monohydrate, process for making same and pharmaceutical compositions," issued on October 3, 2000. It protects the nasal spray Nasonex, which uses mometasone furoate monohydrate ("MFM") as a suspension in water for the treatment of various nasal allergic symptoms.

Prior to Merck’s development of MFM, a Merck chemist first synthesized and patented in the 1980s anhydrous mometasone furoate ("MFA"), which was used to develop a treatment of psoriasis, a skin condition. In the late 1980s, a Merck formulator led a project to develop mometasone furoate for nasal applications, which led to the development of MFM. MFA and MFM are both polymorphs, but have different molecular structures.

Amneal’s ANDA. Amneal filed an Abbreviated New Drug Application ("ANDA") seeking to produce and market a generic mometasone furoate nasal spray, using MFA as the active pharmaceutical ingredient, not MFM. Amneal’s product has a proposed shelf life of two years. Merck’s infringement claim did not allege that the pre-formulation active pharmaceutical ingredient in Amneal’s product contains MFM or otherwise infringes the ‘353 Patent. Instead, it alleged, according to the court, that the MFA in Amneal’s product "will eventually convert to MFM," within the product’s two-year shelf life.

Thermodynamic study. The court held a two-day bench trial on June 21 and 22, 2016, at which the parties presented expert testimony concerning testing of the Amneal product. Using samples of Amneal’s ANDA product, Merck’s expert conducted a thermodynamic stability test, which he testified showed that "conversion will occur" from the MFA to MFM, though it did not establish when it would occur. In the testing, Merck’s expert added MFM to the MFA in one of the samples, which Amneal’s expert opined "changed the rate of nucleation" and the kinetics, such that the formulated product "now had a crystal form that it preferred." The parties’ experts disputed what the testing showed, with Merck’s expert showing conversion would occur, while Amneal’s testifying that the conversion from MFA to MSM "is difficult, as there is a high energy barrier," according to the court.

The court concluded that "generally additional (or faster) mixing tends to promote conversion from MFA to MFM." However, the court found that neither party quantified how additional (or faster) mixing might affect the dissolution of MFA, or the growth of MFM in Amneal’s product, and that the thermodynamic study did not inform that determination. Thus, it denied Merck’s request for further testing of additional samples and a new trial.

Raman spectroscopy. Merck tested batches of Amneal’s product using a Renishaw Raman spectrometer. The court explained that Raman spectroscopy is a "vibrational spectroscopy technique, which looks at the way a molecule vibrates in crystal." A Raman spectrum is created, which indicates the vibrational modes of molecules and can differentiate between crystalline forms. Merck’s expert tested samples from four bottles of Amneal’s products, agreeing that he did not find MFM in any of the samples, and that some of the tested samples were more than two years old. Merck thus contended that the bottles tested were not representative of Amneal’s ANDA product, but the court found that the testing of those samples was relevant to infringement.

While Merck’s expert testified to identifying MFM crystals on three of seven slides taken from one of the samples, Amneal’s expert countered that what was seen was indicative of MFA and "could easily be misinterpreted" and "be misrepresented as MFM." Amneal’s expert concluded that MFM was not present. Merck’s expert had used "one peak," and Amneal’s expert countered that "three peaks" is necessary to provide "absolute confirmation" of MFM’s presence, so that Merck’s testing was inadequate. The court noted that in a prior federal court decision from New Jersey, the court "concluded (based on expert testimony) that at least three peaks on a spectra must be used to identify material based on accepted practices." (Citing Schering Corp. v. Apotex, Inc., 2012 WL 2263292 (D.N.J. June 15, 2012)). Thus, the court assigned "little weight" to Merck’s expert’s findings.

Next, the court addressed the testing by Amneal’s expert, which Merck’s expert criticized as only indicating whether MFM was present at the time of testing, not whether it may form during the product’s proposed two-year shelf life. The court pointed out that neither expert opined on a "growth rate" for MFM from MFA. Therefore, the court found that Amneal’s expert’s testing "is as least as relevant as the conclusions drawn by" Merck’s. With the two sides’ expert testimony effectively cancelling each other out, the court concluded that Merck did not carry its burden to prove by a preponderance of the evidence that MFM is present in Amneal’s product during its two-year shelf life. Thus, it found for Amneal and held that its product does not infringe the ‘353 Patent.

The case is No. 1:15-cv-00250.

Attorneys: Jack B. Blumenfeld and Derek J. Fahnestock (Morris, Nichols, Arsht & Tunnell LLP) and Nicolas Barzoukas, Joshua Davis, Kevin E. Cadwell, and Lisa M. Thomas (Reed Smith LLP) for Merck Sharp & Dohme Corp.

Anne Shea Gaza, Robert M. Vrana, and Samantha G. Wilson (Young Conaway Stargatt & Taylor, LLP) and Constance S. Huttner, Michael H. lmbacuan, Stephanie J. Kamerow, and Caroline Sun (Budd Larner, P.C.) for Amneal Pharmaceuticals LLC.

Companies: Merck Sharp & Dohme Corp.; Amneal Pharmaceuticals LLC

MainStory: TopStory Patent DelawareNews

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