The U.S. Court of Appeals for the Federal Circuit affirmed a district court decision that Apotex and Impax infringed on patents covering AstraZeneca’s heartburn drug Prilosec.  In re Omeprazole Patent Litigation (Astrazeneca v. Apotex Corp., Apotex and Impax; 07-1414, -1416, -1458, -1459).  This ruling comes on the heels of its earlier affirmation of a decision by the U.S. District Court for the Southern District of New York finding that Mylan and Esteve did not infringe on the same patents.

This is part of a consoldation of suits by AstraZeneca against a number of generic drug manufacturers for infringement of Astra’s patents, U.S. Patent No. 4,786,505 and U.S. Patent No. 4,853,230, covering formulations of omeprazole, the active ingredient in Prilosec, a drug designed to treat acid-related gastrointestinal disorders.  The companies were two of several firms to file ANDAs for the drug.

The district court consolidated several of the Prilosec cases and heard arguments in a 42-day bench trial. The court found for AstraZeneca, rejecting the defendants’ arguments for making the effective date of their ANDAs earlier than Oct. 20, 2007. The patents had expired April 20, 2007.

The patents relate to pharmaceutical preparations containing omeprazole, the active ingredient in Prilosec.  Omeprazole is a strong inhibitor of gastric acid secretion, but it is susceptible to degradation in acid-reacting and neutral media.  Its stability is also affected by moisture and organic solvents.

To increase the storage stability of a pharmaceutical dosage, alkaline reacting compounds (ARCs) may be added to the drug core.  The addition of an ARC, however, can compromise the enteric coating.

The inventors of the ’505 and ’230 patents solved that problem by adding an inert subcoating that rapidly disintegrates in water.  The subcoating increases storage stability and provides sufficient gastric acid resistance to prevent omeprazole from degrading in the stomach.  Once the dosage reaches the small intestine, the solubility of the subcoating allows for rapid release of the omeprazole in the drug core.

Impax argued that the district court lost jurisdiction over the case after the patents expired on April 20, 2007.  Impax argued that on that date the case became moot because Astra, having already dismissed its claims for damages, had no remaining claim for any possible relief to which it might be legally entitled.

The district court rejected that argument because the FDA had granted Astra an additional six-month period of market exclusivity after Astra had agreed to the FDA’s request that it perform pediatric testing of its product.  The court held that it had the authority to enforce Astra’s right to market exclusivity under the authority of section 271(e)(4)(A) and under its general equitable authority.

Section 271(e)(2)(A) makes it an act of infringement to file an application under section 505(j) of the Federal Food, Drug, and Cosmetic Act or described in section 505(b)(2) of such Act for a drug claimed in a patent or the use of which is claimed in a patent.

In most circumstances, the effective date in a district court’s order under section 271(e)(4)(A) will be the date of patent expiration, including any patent extensions.  In this case, however, Astra was entitled to an additional six-month period of market exclusivity (pediatric exclusivity) under the Food and Drug Administration Modernization Act of 1997.

The Act authorizes the FDA to make a written request to the holder of an approved new drug application (NDA) for the holder to perform pediatric studies.  If the NDA holder agrees and performs the pediatric studies, the period during which the FDA is barred from approving an ANDA filed by competing drug manufacturers is extended by six months.

The Federal Circuit sided with the district court:

Impax does not dispute that, if the district court had issued its decision before the patents expired, section 271(e)(4)(A) would have authorized the district court to order the effective date of Impax’s ANDA to be October 20, 2007, the date on which Astra’s period of market exclusivity expired.  Impax argues that once the patents expired, section 271(e)(4)(A) no longer provided a remedy because the patents’ expiration rendered the claim of infringement moot.  That argument simply assumes its conclusion; Impax offers no reason to suggest that section 271(e)(4)(A) provides no remedy after patent expiration other than to assert that no remedy is available after patent expiration.

Impax also challenged the district court’s findings with respect to the public-use bar under section 102(b).  Astra filed its applications for the ’505 and ’230 patents on April 20, 1987.  The critical date of the patents is therefore April 20, 1986.  Before that date, Astra commissioned four large clinical studies to determine the safety and efficacy of its formulation in order to obtain FDA approval.

Impax argued that the studies involved the public use of Astra’s claimed formulation.  The district court ruled against Impax on two grounds.  First, the court ruled that the studies constituted experimental uses, and therefore not public uses, of the claimed invention.  Second, the court ruled that the patented formulation was not ready for patenting until after the studies were completed.

The CAFC agreed with Impax that the district court misapplied this circuit’s law with respect to the experimental use exception since experimental use cannot negate a public use when it is shown that the invention was reduced to practice before the experimental use.

However, the CAFC affirmed the district court’s conclusion that the claims were not invalid under section 102(b) based on the court’s factual determination that the claimed formulation was not ready for patenting until after the clinical studies were completed.  That is, the claimed formulation was not reduced to practice before the clinical trials were completed.

In Pfaff, the Supreme Court described two ways for a party to show that an invention was ready for patenting before the critical date of section 102(b): “by proof of reduction to practice before the critical date; or by proof that prior to the critical date the inventor had prepared drawings or other descriptions of the invention that were sufficiently specific to enable a person skilled in the art to practice the invention.”

To demonstrate reduction to practice, a party must prove that the inventor (1) constructed an embodiment or performed a process that met all the limitations and (2) determined that the invention would work for its intended purpose.

Despite Impax arguing that it was known in 1979 that omeprazole could provide a safe and effective treatment, the CAFC shot down that theory:

The Astra scientists had long understood that omeprazole could provide a safe and effective treatment for certain gastrointestinal diseases.  The challenge they faced was developing a formulation to deliver omeprazole to the small intestine, a challenge that was made difficult by omeprazole’s sensitivity to acidic environments, such as the stomach.  Impax has not demonstrated that, without conducting the Phase III clinical tests, the inventors knew that the Phase III formulation would achieve the goals of long-term stability and in vivo stability such that it would be effective as a treatment for gastrointestinal disease.  We therefore find no clear error in the district court’s finding on this issue.

See also: AstraZeneca Suffers Reflux Over Generic Omeprazole

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