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“Second best choice” does not teach away – ZEGERID

omeprazole / sodium biocarbonate

On September 4, 2012, the Court of Appeals for the Federal Circuit issued its per curiam opinion in Santarus v. Par Pharmaceutical. The matter involves U.S. Patent Nos. 6,489,346, 7,399,772, 6,780,882, 6,699,885 and 6,645,988 variously listed in the Orange Book against Santarus’ ZEGERID brand of omeprazole / sodium bicarbonate capsules and powder for oral suspension.  The patents are owned by the University of Missouri and are exclusively licensed to Santarus.

Background

Each of the asserted patents, which are members of the same patent family, are generally directed to methods for treating an acid-caused gastrointestinal disorder comprising administering a solid pharmaceutical composition in a dosage form that is not enteric coated.

One of the asserted patents, the ‘722 patent, claims a method for treating and acid-caused gastrointestinal disorder comprising administering a solid pharmaceutical composition wherein the composition does not contain sucralfate. While the ‘722 patent discloses that sucralfate has certain disadvantages as a therapeutic agent, the District Court held that it was necessary for the ‘722 specification to include evidence demonstrating that sucralfate was “contraindicated” in order to meet the written description requirement under 35 USC § 112.

The District Court found that a break in priority allowed  U.S. Patent No 5,840,737  to be cited as prior art against a some of  the asserted claims and that all such claims were rendered obvious by the ‘737 patent.  The District Court also found that all of the asserted claims were  invalid for obviousness in light of two prior art references, Pilbrant and Lamer, each of which taught that uncoated omeprazole formulations containing sodium bicarbonate buffer could be used as an alternative to enteric coating in order to protect omeprazole from degrading in the stomach.

CAFC – Written Description

The majority (Judges Rader and Moore) held that the negative claim limitation of the ‘722 patent is adequately supported when the specification describes a reason to exclude the relevant limitation.  In this case, statements in the disclosure listing the disadvantages of using sucralfate were sufficient to support the “no sucralfate” claim limitation.

Judge Newman agreed that the District Court judge had erred in finding inadequate written description but dissented with the majority’s “gratuitous fillip” requiring the specification to disclose the reason for a claim limitation, holding:

The panel majority is incorrect in its new general requirement that the reason for any negative limitation must be included in the specification, on pain of invalidity under §112. This new ground of invalidity ignores the factual nature of the written description requirement, and impugns the presumption of validity of a duly granted patent. The court’s new rule simply adds to the uncertainty of the patent grant, to the detriment of invention and commerce.

CAFC – Obviousness

a. Claims for which the ‘737 patent is prior art

The majority concluded that the ‘737 patent, which teaches the omeprazole does not need to be enteric coated, is prior art against some of the asserted claims. While the prior art before the ‘737 patent had taught away from tablets, capsules and granules with non-enteric coated omeprazole, the majority held that the ‘737 patent expressly teaches these formulations. The majority thus concluded the District Court had correctly found that claims for which the ‘737 patent was prior art were obvious.

Judge Newman, in dissent, held that the earlier applications from which priority was properly claimed cannot be cited has prior art against the later-filed ‘885, ‘998 and ‘346 and ‘722 patents.

b. Claims for which the ‘737 patent is not prior art

The parties disputed whether the prior art taught away from the use of non-enteric coated oral dosage forms of proton pump inhibitors (PPIs). The majority concluded that Pilbrant taught away from conventional oral dosage forms (e.g. tablets, capsules, or granules) with non-enteric coated PPIs and reversed the District Court’s obviousness findings in respect to claims limited to such dosage forms (claims 4, 5, 8, 10, 12, 14 and 15 of the ‘772 patent).  Pilbrant, however, did not teach away from alI non-enteric omeprazole formulations. Relying on a passage in Pilbrant disclosing that a “rapidly dissolving suspension of micronized omeprazole is the second best choice as the reference formulation” the majority concluded:

Pilbrant thus teaches that, although suspensions of buffered non-enteric coated omeprazole may be the “second best choice,” they are a viable alternative to enteric coating. “A statement that a particular combination is not a preferred embodiment does not teach away absent clear discouragement of that combination.” Syntex (U.S.A.) LLC v. Apotex, Inc., 407 F.3d 1371, 1380 (Fed. Cir. 2005). Describing a formulation as “second best” is not a “clear discouragement,” as is required by our precedent.

Thus, Pilbrant discloses, and does not teach away from, “a powder that can be combined with an aqueous medium then orally administered.” For the claims that are broad enough to include this powder (i.e., those not limited to tablets, capsules, or granules), the solid pharmaceutical dosage limitation is taught by Pilbrant.

The majority further concluded that Pilbrant renders obvious certain claims that include additional limitations directed to the relative amounts of the PPI and buffer in the pharmaceutical composition (claims 58-60 of the ‘346 patent and claims 12 and 27 of the ‘822 patent). Other claims requiring certain amounts of buffering agents (claims 20 and 21 of the ‘722 patent and claims 11 and 15 of the ‘882 patent) were not rendered obvious by Pilbrant.

The majority also concluded that the District Court’s factual findings on Santarus’ objective evidence of nonobviousness, including a finding of no commercial success, was entitled to deference and that this evidence was insufficient to overcome the obviousness of the claims in light of Pilbrant.

Judge Newman, in dissent, held that the majority had mischaracterized the teaching of Pilbrant and failed to mention a plethora of patents and publications that uniformly stated that the PPI must be enteric coated, holding:

The prior art and the expert witnesses were explicit and uniform, that benzimidazole PPIs require an enteric coating for practical oral administration to patients. Proceeding contrary to the accepted scientific knowledge is “strong evidence of nonobviousness.” W.L. Gore & Associates, Inc. v. Garlock, Inc., 721 F.2d 1540, 1552 (Fed. Cir. 1983). There was no evidence contrary to the position that an enteric coating was believed to be necessary.

This is a classical example of “teaching away,” when persons in the field of the invention “would be led in a direction divergent from the path that was taken by the applicant.” Ricoh Co., Ltd. v. Quanta Computer Inc., 550 F.3d 1325, 1332 (Fed. Cir. 2008). The principal reference relied on by the panel majority concluded that an “enteric-coated dosage form, which releases omeprazole for absorption in the small intestine . . . offers the best possibilities.” Pilbrant, at 114-15. This conclusion was repeated in a patent of which Dr. Pilbrant is an inventor, entitled “Pharmaceutical Preparation for Oral Use.” This patent refers to the studies in the Pilbrant article, and states:

From what is said about the stability properties of omeprazole [in the article], it is obvious that an oral dosage form of omeprazole must be protected from contact with the acid reacting gastric juice in order to reach the small intestine without degradation.

The District Court’s judgment was affirmed-in-part, reversed-in-part and remanded for further proceedings consistent with the Court of Appeals’ opinion.

A copy of the Court of Appeals’ opinion may be found here.

A copy of the District Court’s judgment may be found here.

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