Schering Corp. v. Apotex Inc.

Case Name:  Schering Corp. v. Apotex Inc., C.A. No. 09-6373 (PGS), 2012 U.S. Dist. LEXIS 83414 (D.N.J. June 15, 2012) (Sheridan, J.)

Drug Product and Patent(s)-in-Suit: Nasonex® (mometasone furoate monohydrate); U.S. Patent No. 6,127,353 ("the '353 patent")

Nature of the Case and Issue(s) Presented:  Claim 1 of the '353 patent claims mometasone furoate monohydrate, the active ingredient in Schering's Nasonex product.  Claim 11 of the '353 patent claims the use of mometasone furoate monohydrate in a nasal spray formulation.  The active ingredient in Apotex's ANDA product is mometasone furoate anhydrate.  Apotex bases its non-infringement argument on the fact that its ANDA product is different from Nasonex because it intends to manufacture a nasal spray that contains mometasone furoate anhydrous-as opposed to monohydrate.  The '353 patent also discloses testing methods to determine whether a compound contains mometasone furoate monohydrate.  Schering's infringement proof therefore boils down to whether the Apotex ANDA product contains any of the monohydrate as determined by the testing methods in the '353 patent, namely, water analysis, X-ray particle diffraction, and infrared spectroscopy.  The Court held that Schering did not show by a preponderance of the evidence that Apotex infringed the asserted claims of the '353 patent.  Apotex also claimed that the '353 patent was invalid as anticipated and obvious, but the Court rejected those arguments.

Why Apotex Prevailed:  Schering retained an expert to analyze the Apotex ANDA product to determine whether it converted from an anhydrate to a monohydrate between the date of manufacture and its expiration date, i.e., two years.  One of the problems, however, was that the testing of Apotex ANDA products did not occur until the samples were near or beyond the two-year time period that such a conversion was theorized to have taken place.  Schering's expert also had to remove other excipients from Apotex's product through a process of shaking or heating in order to have a more sensitive depiction of the active drug during testing.  In the end, Schering's expert did not convince the Court that either the sample prep (the washing and shaking of the Apotex product resulting in undermining the stability of the compound) or the testing results (which lacked the critical three-peak graph indicating presence of the monohydrate) showed a conversion to the monohydrate form.  In addition to relying on testimony from Apotex's expert that the "Apotex formulation would be stable against conversion to the monohydrate for around 800 years," the Court gave weight to Apotex's expert and his connotation that Schering's expert "overstepped the boundaries of a disciplined scientist."

As to Apotex's invalidity contentions, the Court made the following findings.  Until the discovery of mometasone furoate monohydrate reflected in the '353 patent, the only known form of mometasone furoate was the anhydrous form.  The conversion of anhydrous mometasone furoate to the monohydrate form did not occur in all formulations, and appeared to be unpredictable.  The '353 patent application was rejected several times during prosecution on the basis of the Shapiro reference.  The Patent Office did not see anything new in converting an anhydrate to a monohydrate-"according to the reviewer, it was just adding water."  Shapiro disclosed a process involving recrystallization of mometasone furoate crystals from methanol: water, and that process, according to the Patent Examiner, inherently contained the monohydrate form.  After three rejections based on Shapiro, Schering produced an infrared IR spectrum of the recrystallization compound from Shapiro patent files, which lacked prevalent water peaks.  This resulted in the '353 patent application's issuance.  With regard to Apotex's anticipation argument, because it was not raised in the pretrial order, the Court held that Apotex waived its defense.  Apotex's obviousness argument claimed that a person of ordinary skill in the art would have been motivated to develop a nasal spray using mometasone furoate, the compound first described in Shapiro.  The Court disagreed.  The court held that there was no motivation or reason to develop a nasal spray using mometasone furoate because the metabolism of mometasone furoate in the liver was unknown and, therefore, a person of ordinary skill in the art would have had a "major concern about the systemic effects of nasal delivery of the drug."