The Federal Circuit decision in AstraZeneca LP v. Apotex, Inc. reveals an interesting dichotomy in the role of printed material in pharmaceutical patent disputes. On the one hand, the court found that proposed labeling for Apotex’s drug product supported a claim of induced infringement, while on the other it confirmed that the labeling included in AstraZeneca’s kit claims are not given patentable weight when assessing validity.

This case reached the Federal Circuit as Apotex’s appeal from the district court’s grant of a preliminary injunction barring Apotex from marketing its generic product, and AstraZeneca’s appeal from the district court’s ruling that its kit claims are invalid.

AstraZeneca’s Innovator Product

The dispute surrounds AstraZeneca’s budesonide product marketed as Pulmicort Respules®. AstraZeneca’s product is available in 0.25 mg, 0.5 mg and 1.0 mg strengths. The Orange Book listing cites three patents, including two at issue in this case:

U.S. 6,598,603, directed to methods of “treating a patient suffering from a respiratory disease, the method comprising administering to the patient a nebulized dose of a budesonide composition in a continuing regimen at a frequency of not more than once per day.”

U.S. 6,899,099, directed to methods of “treating a patient suffering from a respiratory disease, the method comprising administering to the patient a nebulized dose of a budesonide composition in a continuing regimen at a frequency of not more than once per day, wherein the administration is in the evening.”

(The third patent, U.S.7,524,834, is directed to a micronized powder composition of budesonide.)

As noted by the Federal Circuit, although AstraZeneca’s patents recite once daily administration, the labeling on AstraZeneca’s product contemplates administration once or twice a day. The labeling also indicates that patient doses should be titrated down to the lowest effective dose.

Apotex’s Generic Product

Apotex sought FDA approval for a generic budesonide product for twice daily use. Apotex submitted a “carve-out” statement under 21 USC § 355(j)(2)(A)(viii) with regard to the once daily methods of the AstraZeneca patents. This portion of the ANDA statute provides:

[I]f with respect to the listed drug referred to in clause (i) information was filed under subsection (b) or (c) of this section for a method of use patent which does not claim a use for which the applicant is seeking approval under this subsection, a statement that the method of use patent does not claim such a use.

Apotex’s product would be available in 0.25 mg and 0.5 mg strengths. The FDA required Apotex’s label to include the same downward-titration language as AstraZeneca’s label, but it did not include any explicit mention of once daily use.

Words That Matter: Apotex’s Drug Product Label

The district court found that Apotex’s label would induce some patients to infringe AstraZeneca’s patents. For example, the label lists “starting” daily doses of 0.5 mg “administered twice daily in divided doses.” As noted above, the label also states that “it is desirable to donward-titrate to the lowest effective dose.” Given that the lowest available strength was going to be 0.25 mg, the only way to titrate down from a 0.5 mg daily dose would be to use the 0.25 mg strength product once a day, as claimed in the AstraZeneca patents.

The district court also found that the inclusion of the downward-titration language in Apotex’s labeling provided evidence of Apotex’s specific intent to induce infringement.

The Federal Circuit agreed:

The pertinent question is whether the proposed label instructs users to perform the patented method. If so, the proposed label may provide evidence of Apotex’s affirmative intent to induce infringement.

The court noted that the downward-titration language was “applicable to the recommended starting doses and . . . would inevitably lead some consumers to practice the claimed method.”

The Federal Circuit rejected Apotex’s arguments that the label could not provide sufficient evidence of intent because it was required by the FDA. The court agreed with AstraZeneca’s position that “if Apotex could not create a noninfringing label, Apotex should have waited for the [AstraZeneca] patent to expire before attempting to market its generic drug.”

Thus, the Federal Circuit upheld the district court’s finding that AstraZeneca established a likelihood of success on the merits of its inducement claim.

Words That Don’t Matter: AstraZeneca’s Kit Labeling

Both AstraZeneca patents include similar kit claims:

The ‘603 patent included kit claims directed to kits for “treating respiratory diseases, the kit comprising (a) a budesonide composition in a sealed container, the composition containing 0.05 mg to 15 mg budesonide and a solvent, and (b) a label indicating administration by nebulization in a continuing regimen at a frequency of not more than once per day.”

The ‘099 patent included kit claims directed to kits for “treating a respiratory disease, the kit comprising (a) a budesonide suspension in a sealed container, the suspension containing 0.05 mg to 15 mg budesonide and a solvent, and (b) a label indicating administration by nebulization in a continuing regimen at a frequency of not more than once per day.”

The budesonide composition recited as component (a) of each kit was known in the art. Thus, the claims would be invalid unless the label components are entitled to patentable weight.

AstraZeneca argued that the label language should be considered when assessing validity because of the special relationship between a drug and its label which makes them “inextricably interrelated.” For example, “a drug cannot be approved unless and until the FDA approves its label.”

The Federal Circuit noted that printed mater generally falls outside the scope of patent-eligible subject matter circumscribed by 35 USC 101, unless there is a “‘functional relationship’ between the printed matter and its substrate.”

According to the court, the facts here fell squarely under the 2004 case of In re Ngai. In that case, like here, the only difference between the claimed invention and the prior art was the instructions. Because “the printed matter in no way depends on the kit, and the kit does not depend on the printed matter,” the “claimed instructions are not entitled to patentable weight.”

The court acknowledged that “FDA regulations require a label containing information needed for the safe and effective use of any drug” but emphasized that “this is a requirement for FDA approval, not patentability.”

Thus, the Federal Circuit affirmed the district court’s holding that the kits claims are invalid.

Weigh Your Words

This case underscores the different roles that labeling can play in pharmaceutical patent disputes. From Apotex’s perspective, its product labeling may have been given too much weight, supporting liability for induced infringement, while from AstraZeneca’s perspective, its kit labeling was not given enough weight, leading to the invalidation of the kit claims. Both outcomes serve as a reminder to chose your words carefully, and consider the weight they may be given in different circumstances.