Summary judgment, while clearly advantageous, requires that there be no disputed question of material fact and that the moving party is entitled to judgment as a matter of law.  When a district court grants judgment improvidently, by misapplying the law, judgment can be reversed and the matter returned to the court for proceedings under the correct application of the law.  These are the circumstances that resulted in the opinion of the Federal Circuit in Valeant Pharmaceuticals Int'l v. Mylan Pharmaceuticals Inc.

This ANDA litigation arose over Defendants' attempt to obtain regulatory approval under the Hatch-Waxman Act for generic formulations of Relistor® (methylnaltrexone), in particular ones having certain stability properties that the inventors of the Orange Book-listed patents had shown depended on the pH of the formulation.  In particular, methylnaltrexone is stable in aqueous solution when the pH of the formulation is adjusted to remain between 3 and 4.  U.S. Patent No. 8,552,025 recites claims to such formulations; claim 8 was at issue in the litigation:

1.  A stable pharmaceutical preparation comprising a solution of methylnaltrexone or a salt thereof, wherein the preparation comprises a pH between about 3.0 and about 4.0.

8.  The pharmaceutical preparation of claim 1, wherein the preparation is stable to storage for 24 months at about room temperature.

ANDA plaintiff Valeant brought suit, and Defendant Mylan stipulated to infringement but contended that asserted claim 8 was obvious, under a stipulated claim construction that "the phrase 'the preparation is stable to storage for 24 months at about room temperature' means 'the methylnaltrexone degradation products in the preparation do not exceed 2.0% of the total methylnaltrexone present in the preparation and the preparation is suitable for pharmaceutical use when stored for 24 months at room temperature.'"  The District Court granted Valeant's motion for summary judgment; in doing so, the court "rejected Mylan's expert testimony and cited references as being insufficient, largely because the references did not teach methylnaltrexone formulations but instead formulations of similar but different compounds, naloxone and naltrexone."  In addition, the District Court rejected Mylan's second argument that using the claimed pH range would have been obvious to try.

On appeal the Federal Circuit reversed and remanded, in an opinion by Judge Lourie joined by Judges Reyna and Hughes.  Relevant to the panel's decision (unavoidable perhaps in view of Judge Lourie's background in chemistry), the opinion notes the resemblances between methylnaltrexone and the prior art compounds naltrexone and naloxone; as set forth in the opinion, these differences are small:

The only structural difference between these three molecules is the identity of the functional group attached to the nitrogen atom.  Naloxone is a neutral tertiary amine.  Naltrexone, also a neutral tertiary amine, has a cyclopropylmethyl group attached to the nitrogen.  Methylnaltrexone, a derivative of naltrexone, is a quaternary ammonium salt and has both a cyclopropylmethyl group and a methyl group attached to its nitrogen with a positive charge.

The District Court summarily dismissed Mylan's argument regarding the prior art due to these differences, basing its conclusion on the grounds that what the art taught for naloxone and naltrexone would not have provided sufficient guidance to the skilled worker to appreciate that the prior art teachings would be relevant to methylnaltrexone.  This basis for the District Court's decision is important because one reference, U.S. Patent No 5,866,154, taught that naloxone formulations were stabilized at pH 3.0-3.5, and another, U.S. Patent Application Publication No. 2003/0229111, taught that naltrexone formulations could be stabilized with various organic acids (including butylated hydroxytoluene and ascorbic acid) having a pH adjusted to between 3 and 5 but preferably pH 4.  In addition, there were pharmaceutical treatises teaching the benefits of maintaining the pH for formulations of this general class of compounds at acidic pH.

The Federal Circuit held that the District Court's disregard for the prior art on this basis was error, and found that Mylan had asserted a prima facie case of obviousness precluding summary judgment, citing In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (citing In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997)); In re Woodruff, 919 F.2d 1575, 1578 (CCPA 1990); and In re Malagari, 499 F.2d 1297, 1303 (CCPA 1974), in support of its decision to reverse.  The opinion states that such a prima facie case exists when there is, as here, an overlap in ranges of a property or characteristic of a claimed composition.

The Court recognized the underlying question of "whether prior art ranges for solutions of structurally and functionally similar compounds that overlap with a claimed range can establish a prima facie case of obviousness," holding that "they can, and in this case, do."  Structurally similar compounds are expected by skilled artisans to have similar properties, according to the opinion, citing Daiichi Sankyo Co. v. Matrix Labs., Ltd., 619 F.3d 1346, 1352 (Fed. Cir. 2010), citing In re Dillon, 919 F.2d 688, 692 (Fed. Cir. 1990) (en banc); In re Deuel, 51 F.3d 1552, 1558 (Fed. Cir. 1995); In re Merck & Co., Inc., 800 F.2d 1091, 1097 (Fed. Cir. 1986); Application of Payne, 606 F.2d 303, 314 (CCPA 1979); In re Wood, 582 F.2d 38, 641 (CCPA 1978); and Application of Rosselet, 347 F.2d 847, 850 (CCPA 1965).  The opinion recognizes that this case law focuses on compounds and uses thereof, but the Court maintained that "the principle established in these cases applies more broadly: a person of skill in the art can expect that compounds with common properties are likely to share other related properties as well," citing Anacor Pharms., Inc. v. Iancu, 889 F.3d 1372, 1384 (Fed. Cir. 2018).  Further, relevant to the question before the panel, "[w]hen compounds share significant structural and functional similarity, those compounds are likely to share other properties, including optimal formulation for long-term stability."  The opinion then recites the similarities between the prior art naloxone, naltrexone, and methylnaltrexone, including that they are all opioid antagonists and bind to opioid receptors but don't activate them; and that they are all oxymorphone derivatives with only minor structural variations limited to substituents attached to the same nitrogen atom (naloxone and naltrexone being uncharged tertiary amines differing by substitution of a cyclopropylmethyl group in the latter, while methylnaltrexone is a charged, quaternary ammonium salt substituted by both a cyclopropylmethyl group and a methyl group).  According to the opinion, "[b]ecause of the strong structural and functional similarity between the molecules, a person of skill could expect similar stability of the molecules at similar pH ranges in solution" (a conclusion that seems inconsistent with the significant differences, inter alia, with the molecule comprising the claimed formulation being positively charged at neutral pH while the compounds comprising the prior art formulations were not).

But the opinion makes the point that the District Court erred because the similarities were sufficient to preclude summary judgment.  It makes the further point that the Federal Circuit's opinion should not be construed to mean that "molecules with similar structure and similar function can always be expected to exhibit similar properties for formulation."  Rather, the case deserved to be tried to a factfinder (here, the District Court) to determine whether Valeant can overcome Mylan's prima facie obviousness case.

The opinion next turned to the District Court's summary rejection of Mylan's obvious-to-try argument.  This rejection was expressly based on the "infinite" values of pH between pH 3 and pH 7 as a matter of "basic math."  Further, the District Court refused to credit Mylan's experts' testimony regarding the skilled artisan's apprehension that adjusting pH could improve stability, because the evidence did not show that adjusting pH would have been the first variable the artisan would have considered.  The District Court further did not accept that improved long-term methylnaltrexone stability would be a predictable result of adjusting formulation pH to between 3 and 4.

The Federal Circuit reversed the District Court on this argument as well, citing the eternal aphorism from KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421 (2007) that "[w]hen there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp."  For Judge Lourie and the panel, the "bounded range of pH 3 to [pH]4" fell within the scope of the Supreme Court's teachings as a "finite number" of pH values for the skilled artisan to try.  While it may be a matter of math that there are an infinite number of numerical values between the numbers 3 and 4, as a practical matter the panel found that there was "no indication that pH is measured to any significant figure beyond two digits."  The panel also found there is no requirement in the law that a variable (to support an obvious-to-try determination) must be the first variable that the skilled artisan would consider.  "Absolute predictability that the proposed pH range would yield the exact stability parameters in the claim is not required," according to the opinion, and thus the District Court erred in granting summary judgment in the face of this argument as well.

The case was sent back to the District Court for further action under the principles set forth in the opinion.

Valeant Pharmaceuticals Int'l v. Mylan Pharmaceuticals Inc. (Fed. Cir. 2020)
Panel: Circuit Judges Lourie, Reyna, and Hughes
Opinion by Circuit Judge Lourie