Esomeprazole & Naproxen - USA

On May 15, 2019, Federal Circuit reversed district court’s decision & found two Vimovo® patents invalid for lack of written description support.

Nuvo/Horizon/Pozen (Plaintiffs) owns US 6,926,907 (expiring on 02/28/2023) and US 8,557,285 (expiring on 05/31/2022) patents.  The two patents bear the same title, “Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs,” and have nearly identical specifications. Dr. Reddy’s Laboratories, Inc., Mylan Pharmaceuticals, and Lupin Pharmaceuticals (Defendants) filed ANDAs to USFDA to market generic version of Vimovo®. Plaintiff initiated suit & following a bench trial district court upheld the asserted claims of US’907 and US’285 as nonobvious under 35 U.S.C. § 103, enabled under 35 U.S.C. § 112, and adequately described under § 112. District court also granted summary judgement of non-infringement with respect to Dr. Reddy’s second ANDA. Defendants appealed the written description rulings. They did not appeal the obviousness holding, the enablement decision. Plaintiff cross appealed the district court’s grant of summary judgment of non-infringement.

Claim 1 of the ’907 patent reads:

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.

Claim 1 of the ’285 patent reads:

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.

With respect to written description district court rejected all three arguments put forth by Generics. First, the court rejected the “comprising” written description argument. The Generics argued that, because of the “comprising” language in the ’285 patent’s claims, they allow for the drug formulation to include some uncoated naproxen that is released immediately regardless of the pH, which is not supported by the specification and goes against the concept of coordinated release that is at the heart of the patent’s invention.

Second, the district court rejected the “inhibit” written description argument. The Generics contended that, although the patent discloses only delayed release formulations, the claims of the ’285 patent recite a broader undescribed invention, namely sustained release as op-posed to coordinated release of naproxen.

Third, the district court rejected the “efficacy” written description argument. The Generics argued that, if they lose on their obviousness contention, then the claims lack written description support for the claimed effectiveness of uncoated PPI because ordinarily skilled artisans would not have expected it to work and the specification provides no experimental data or analytical reasoning showing the inventor possessed an effective uncoated PPI.

Upon appeal Federal Circuit with respect to “efficacy” argument said that district court’s analysis does not support its conclusion. The district court, after finding that the specification lacks “information regarding the efficacy of uncoated PPIs,” said it was enough that the specification described the immediate release of uncoated PPI and the potential disadvantages of enteric-coated PPI formulations. But that disclosure it pointed to in no way provides support for the claimed efficacy of uncoated PPI. Generics argued that the record evidence demonstrates that a person of ordinary skill in the art would not have known or understood that uncoated PPI is effective. And there is nothing in the specification of the patents-in-suit showing “that the inventor actually invented the invention claimed.” [Centocor, 636 F.3d at 1348 (emphasis added); accord Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc)].

Federal Circuit further said that in light of the fact that the specification provides nothing more than the mere claim that uncoated PPI might work, even though persons of ordinary skill in the art would not have thought it would work, the specification is fatally flawed. It does not demonstrate that the inventor possessed more than a mere wish or hope that uncoated PPI would work, and thus it does not demonstrate that he actually invented what he claimed: an amount of uncoated PPI that is effective to raise the gastric pH to at least 3.5. That conclusion is confirmed by the inventor’s, Dr. Plachetka’s, own testimony at trial during which he admit-ted that he only had a “general concept of coordinated delivery with acid inhibition” using uncoated PPI at the time he filed his first patent application. In this case, the inventor chose to claim the therapeutic effectiveness of uncoated PPI, but he did not adequately describe the efficacy of uncoated PPI so as to demonstrate to ordinarily skilled artisans that he possessed and actually invented what he claimed. And the evidence demonstrates that a person of ordinary skill in the art reading the specification would not have otherwise recognized, based on the disclosure of a formulation containing uncoated PPI, that it would be efficacious because he or she would not have expected uncoated PPI to raise gastric pH. Under those facts, the patent claims are invalid for lack of adequate written description pursuant to § 112.

Federal Circuit thus declined to address the Generics’ alternative argument that the pa-tents are also invalid under § 112. Also Nuvo’s cross-appeal challenging the district court’s grant of summary judgment of noninfringement with respect to Dr. Reddy’s second ANDA product and the ’907 patent found moot.