Eisai Victorious Over Teva and Dr. Reddy’s in Aciphex Compound Patent Case

Includes: ESALY, RDY, TEVA
by: Aaron F. Barkoff

Eisai v. Dr. Reddy's and Teva, Nos. 2007-1397, -1398 (Fed. Cir. 2008)

Patents on chemical compounds are holding up well to obviousness arguments in the Federal Circuit, even after KSR. In an opinion released Monday, the Federal Circuit affirmed the nonobviousness of rabeprazole, the active ingredient in Aciphex.  This follows adecision last year affirming the nonobviousness of pioglitazone, the active ingredient in Actos.

Eisai's (OTCPK:ESALY) U.S. Patent No. 5,045,552 claims rabeprazole and its salts.Rabeprazole is in a class of drugs known as proton pump inhibitors, which suppress gastric acid production in the stomach. Aciphex (rabeprazole sodium) is indicated for the treatment of duodenal ulcers, heartburn, and associated disorders, and accounts for over $1 billion of Eisai's annual sales.

Dr. Reddy's (NYSE:RDY) stipulated to the validity of the '552 patent (relying on inequitable conduct arguments instead), but Teva (NYSE:TEVA) challenged its validity, arguing that a combination of three prior art references rendered the claims of the '552 patent obvious:

  1. European Patent No. 174,726, claiming lansoprazole.
  2. U.S. Patent No. 4,255,431, claiming omeprazole.
  3. An article by Brandstrom et al., entitled "Structure Activity Relationships of Substituted Benzimidazoles."

The Federal Circuit began by summarizing its recent chemical obviousness jurisprudence:

Where, as here, the patent at issue claims a chemical compound, the analysis of the third Graham factor (the differences between the claimed invention and the prior art) often turns on the structural similarities and differences between the claimed compound and the prior art compounds.  Obviousness based on structural similarity thus can be proved by identification of some motivation that would have led one of ordinary skill in the art to select and then modify a known compound (i.e., a lead compound) in a particular way to achieve the claimed compound. In keeping with the flexible nature of the obviousness inquiry, the requisite motivation can come from any number of sources and need not necessarily be explicit in the art. Rather, it is sufficient to show that the claimed and prior art compounds possess a sufficiently close relationship to create an expectation, in light of the totality of the prior art, that the new compound will have similar properties to the old.

With respect to the prior art, the Federal Circuit made the following observations:

  1. Rabeprazole and lansoprazole are structurally similar - the two compounds differ only at the 4-position on the pyridine ring, where lansoprazole contains a fluorinated substituent.
  2. "Omeprazole is structurally farther afield from rabeprazole than is lansoprazole."
  3. Rabeprazole, lansoprazole, and omeprazole are all Brandstrom core structure compounds," a class of anti-ulcerative compounds.

Thus, the Federal Circuit stated, "one of skill in this art may have considered [lansoprazole] a candidate for a lead compound in the search for anti-ulcer compounds. However, according to the court,

The EP '726 reference teaches at best that the fluorinated substituent of lansoprazole provides a special path to achieving lipophilicity, and the record "shows no discernible reason for a skilled artisan to begin with lansoprazole only to drop the very feature, the fluorinated substituent, that gave this advantageous property.

The court concluded that one of skill in the art would not have considered such a modification to be "an identifiable, predictable solution."

Addressing Teva's suggestion that another compound might have served as a lead compound, theFederal Circuit observed that "Teva alone selected lansoprazole as the anchor for its obviousness theory. Moreover, according to the court,

Post-KSR, a prima facie case of obviousness for a chemical compound still, in general, begins with the reasoned identification of a lead compound.  Teva cannot create a genuine issue of material fact on obviousness through the unsupported assertion that compounds other than lansoprazole might have served as lead compounds.

In addition to affirming the validity of the '552 patent, the Federal Circuit affirmed its enforceability, rejecting arguments that Eisai committed inequitable conduct.

Dr. Reddy's and Teva alleged that Eisai misled the Patent Office in five ways:

  1. It failed to disclose Eisai's own co-pending '013 application, which claimed the "ethyl homolog" of rabeprazole.

  2. It withheld rejections from the '013 application's prosecution that also would have been applicable to the '552 patent's prosecution.

  3. It failed to disclose the prior art "Byk Gulden patent."

  4. It submitted a misleading declaration to the examiner of the '552 patent.

  5. It concealing lansoprazole from the examiner.

The Federal Circuit affirmed the district court's findings that:

  • The materiality of the '013 application was "low."
  • There was insufficient evidence that Eisai intended to deceive the Patent Office by failing to disclose the rejections made during prosecution of the '013 application.
  • The Byk Gulden patent was cumulative with other references disclosed to the Patent Office.
  • Eisai did not intend to deceive the Patent Office by submitting the "misleading declaration" during prosecution of the '552 patent.
  • Lansoprazole was not material to the patentability of rabeprazole.

Affirming the district court on all counts, the Federal Circuit concluded,

In a series of thoughtful, thorough opinions, the district court carefully explained its reasoning with respect to both obviousness and inequitable conduct.