There are provisions and interpretations of U.S. patent law that can be in tension depending on the circumstances under which they are argued, whether before an Examiner or during litigation. One of these is the dichotomy between arguing that the prior art would provide insufficient expectation of success to render an invention obvious, while at the same time relying on what was known by a person of skill in the art to minimize the extent of the written description provided in a specification that satisfies the written description requirement of 35 U.S.C. § 112(a). This tension proved fatal to the claims at issue in Nuvo Pharmaceuticals v. Dr. Reddy's Laboratories, decided by the Federal Circuit last week.
The case arose as ANDA litigation against Dr. Reddy's Labs (and Mylan and Lupin entities) over non-steroidal anti-inflammatory drugs (NSAIDs) formulated to diminish recognized gastrointestinal irritation side effects these drugs can cause, the formulations being claimed in Orange Book-listed U.S. Patent Nos. 6,926,907 and 8,557,285 and sold by Nuvo as Vimovo®. The prior art disclosed efforts to avoid these side effects by co-administration of NSAIDs with proton pump inhibitors (PPIs), because stomach acid was believed to contribute to them. These efforts were disadvantageous, inter alia, because stomach acid degraded the PPIs before they could be absorbed in the small intestine and have their acid-diminishing effect in the stomach. The art showed attempts to remedy these shortcomings by enterically coating PPIs to resist stomach acid. These efforts did not entirely fix the problem because the NSAID was degraded if released into the stomach before the PPI could reduce stomach acid (i.e., raising the pH by inhibiting the proton pump responsible for producing the acidic environment therein).
The inventor of the '907 patent invented a new formulation that "coordinated the release of an acid inhibitor and an NSAID in a single tablet, the formulation comprising a core of an NSAID, enterically coated so that the coating dissolves only at an elevated pH, and then providing an amount of a PPI sufficient to provide pH elevated to the enteric cost dissolving level." Claim 1 of the '907 patent and claim 1 of the '285 patent are each set forth as representative in the Federal Circuit's opinion, respectively:
1. A pharmaceutical composition in unit dosage form suitable for oral administration to a patient, comprising:
(a) an acid inhibitor present in an amount effective to raise the gastric pH of said patient to at least 3.5 upon the administration of one or more of said unit dosage forms;
(b) a non-steroidal anti-inflammatory drug (NSAID) in an amount effective to reduce or eliminate pain or inflammation in said patient upon administration of one or more of said unit dosage forms;
and wherein said unit dosage form provides for coordinated release such that:
i) said NSAID is surrounded by a coating that, upon ingestion of said unit dosage form by said patient, prevents the release of essentially any NSAID from said dosage form unless the pH of the surrounding medium is 3.5 or higher;
ii) at least a portion of said acid inhibitor is not surrounded by an enteric coating and, upon ingestion of said unit dosage form by said patient, is released regardless of whether the pH of the surrounding medium is below 3.5 or above 3.5.
1. A pharmaceutical composition in unit dosage form comprising therapeutically effective amounts of:
(a) esomeprazole, wherein at least a portion of said esomeprazole is not surrounded by an enteric coating; and
(b) naproxen surrounded by a coating that inhibits its release from said unit dosage form unless said dosage form is in a medium with a pH of 3.5 or higher;
wherein said unit dosage form provides for release of said esomeprazole such that upon introduction of said unit dosage form into a medium, at least a portion of said esomeprazole is released regardless of the pH of the medium.
While the specification (according to the panel opinion) disclosed many features of the claimed invention, "[i]t is undisputed that there is no experimental data demonstrating the therapeutic effectiveness of any amount of uncoated PPI and coated NSAID in a single dosage form," nor is there any disclosure of formulations wherein uncoated PPI could be used to raise gastrointestinal pH.
The District Court found that Defendants had not shown the asserted claims to be obvious under 35 U.S.C. § 103 nor not enabled or inadequately described under 35 U.S.C. § 112, and that one of Dr. Reddy's generic products did not infringe the '907 patent (granting summary judgment to Dr. Reddy's on its noninfringement motion). Specifically, the Court found that it would not have been obvious to use a PPI according to the asserted claims to prevent gastrointestinal injury from an NSAID, inter alia because the art would have discouraged attempting such formulations due to the known acid sensitivity of PPIs. Moreover, the District Court held that the claims were enabled because the specification disclosed how to make and use the invention. The Court relied on expert testimony in deciding that the skilled worker would have recognized the usefulness of the claimed formulations.
With regard to Dr. Reddy's written description challenges, the District Court found that the use of the transition term "comprising" in the '285 patent claims did not cause the claims to encompass (undisclosed) embodiments having uncoated, immediately released naproxen (an exemplified NSAID). The Court also rejected a second challenge, that the claims encompass sustained-release as well as delayed-release NSAID formulations not supported by the specification, because the claims recited "inhibiting" rather than "preventing" NSAID release prior to achieving the claimed raised pH levels. Finally, the District Court rejected Defendants' argument that "ordinarily skilled artisans would not have expected [the claimed formulation] to work and the specification provides no experimental data or analytical reasoning showing the inventor possessed an effective uncoated PPI." The Court held that "experimental data and an explanation of why an invention works are not required, the specification adequately describes using uncoated PPI, and its effectiveness is necessarily inherent in the described formulation."
This appeal followed, limited to the District Court's findings on the first and third written description arguments; Nuvo cross-appealed on the District Court's grant of summary judgment of non-infringement by Dr. Reddy's second formulation.
The Federal Circuit reversed the District Court's decision and dismissed Nuvo's cross-appeal, in an opinion by Judge Clevenger, joined by Chief Judge Prost and Judge Wallach. The opinion states that the panel's analysis "begins and ends" with Defendants' third written description argument related to a failure to show "efficacy" of the claimed formulation. According to the Federal Circuit, the issue was raised by Nuvo's argument (related to Defendants' obviousness assertions) that "ordinarily skilled artisans would not have expected uncoated PPIs to be effective." Inconsistently, "nothing in the specification would teach a person of ordinary skill in the art otherwise" and this failure to disclose what was not found in the art (and indeed, Nuvo affirmatively contended was not known in the art with regard to the obviousness issue) amounts to a failure to describe how the inventors were in possession of the claimed invention. The District Court's error, according to the Federal Circuit, was that its written description analysis on this point "does not support it conclusions." Because of the "clear error" standard of review imposed on the Federal Circuit on questions of fact (as the adequacy of disclosure sufficient to satisfy the written description requirement is), the opinion asserts that the panel "scour[ed] the record created below for evidence supporting the district court's written description finding."
To no avail. In part, the panel came to this conclusion because they appreciated that Nuvo raised "at least five arguments" ("for the first time on appeal, and as its lead argument") directed to reading any effectiveness language or requirement from the asserted claims. These arguments were, in the panel's view, contradicted by the plain language (and plain meaning thereof) of the claims (claim 1 of the '907 patent recites ". . . in an amount effective to raise the gastric pH of said patient to at least 3.5," and claim 1 of the '285 patent recites ". . . comprising therapeutically effective amounts of "the PPI"; emphasis in the opinion). But the opinion sets forth and rejects each one.
First, Nuvo argued that the dosage form as a whole does not need to be effective in raising gastric pH; the Federal Circuit agreed but did not find any Defendants' argument to the contrary.
Second, Nuvo argued that the claims do not require the NSAID and PPI to be in a single dosage form, but "only amounts of each component effective on their own." Defendants argued that the claim "requires coordinated release achieved by an effective amount of uncoated PPI that raises the gastric pH to at least 3.5 and an effective amount of naproxen that is released to treat pain when the pH reaches the desired level"; the panel held that Nuvo had not presented this argument below and thus it was forfeited.
Third, Nuvo contended that the claim didn't require the uncoated PPI to be effective to raise gastric pH, just that the formulation contained an effective amount of uncoated PPI. In addition to holding Nuvo had also forfeited this argument by not raising it below, the panel termed it "nonsensical to read the claims to require effective amounts of uncoated PPI without specifying the result effectively achieved."
Fourth, Nuvo asserted that the claims encompassed "multiple dosage forms" and thus the specification did not need to expressly describe any particular effective dosage form. Rather than summarily dismissing this argument, the opinion expressly disagreed with it: the '285 patent "does not allow for more than one dosage form" and "[e]ven if it were true that the '907 patent allows more than one dosage form to effectively raise the gastric pH to at least 3.5 using uncoated PPI, the specification would still need to provide support for the notion that uncoated PPI is effective," according to the Court.
Finally, the panel rejected Nuvo's argument that the Examiner interpreted the claims in a manner consistent with their argument, that "the '907 patent claims [] merely require[d] certain amounts of PPI and NSAID effective on their own rather than requiring an overall efficacy for the combined drug." The panel found Nuvo's argument relied in this regard on arguments the Court had already rejected and besides, in their view "the Examiner appears to have interpreted the claims to require an amount of PPI, whether coated or uncoated, effective to raise the gastric pH to the desired level" and that was the written description required (and lacking) in Nuvo's specification.
Having decided what the written description was required to be, the panel then reported its failure in finding support in the specification. Nuvo's attempt to rely on expert testimony was unavailing, in part because this testimony was sufficiently particular that the Court was able to review and reject it. Specifically, the opinion states that "[t]he statements [the expert] points to recite the claim limitation by simply calling generally for effective amounts of uncoated PPI, but our precedent clearly establishes that is not enough . . . . We have expressly rejected the 'argument that the written description requirement . . . is necessarily met as a matter of law because the claim language appears in ipsis verbis in the specification'" according to the opinion, citing Enzo Biochem, Inc. v. Gen–Probe Inc., 323 F.3d 956, 968 (Fed. Cir. 2002). Experimental evidence is not required, In re '318 Patent Infringement Litig., 583 F.3d 1317, 1324 (Fed. Cir. 2009), nor is there any requirement for a "theory or explanation of how or why a claimed composition will be effective," Allergan, Inc. v. Sandoz Inc., 796 F.3d 1293, 1308 (Fed. Cir. 2015), nor does an invention need to be reduced to practice, Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 926 (Fed. Cir. 2004). But here, "there is nothing in the specification of the patents-in-suit showing that the inventor actually invented the invention claimed,'" citing Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1348 (Fed. Cir. 2011) (emphasis in opinion). The Court concluded that the specification is "fatally flawed" with regard to providing an adequate written description of the requisite efficacy recited in the claims, and reversed the District Court's finding that Defendants had not established that the '907 and '285 patents were invalid for failure to satisfy the requirements of 35 U.S.C. § 112.
Nuvo Pharmaceuticals (Ireland) Designated Activity Co. v. Dr. Reddy's Laboratories Inc. (Fed. Cir. 2019)
Panel: Chief Judge Prost and Circuit Judges Clevenger and Wallach
Opinion by Circuit Judge Clevenger
