Opinion ID: 178456
Heading Depth: 4
Heading Rank: 2

Heading: The Thorax Advertisement

Text: As discussed above, a British medical journal published the Thorax advertisement in 1994, more than one year before the filing of the application that issued as the '603 Patent. The advertisement touts AstraZeneca's PULMICORT RESPULES® drug as [a] high-dose nebulised steroid that's low on side effects and notes that the drug can be used to treat bronchial asthma in children. The advertisement indicates that the drug was available in 2 mL single dose vials, each vial containing either 0.25 mg/mL or 0.5 mg/mL of budesonide. The advertisement includes the following statement regarding dosing: Initially . . . the recommended dose in adults . . . is usually 1-2 mg twice daily. . . . Children . . . 0.5-1 mg twice daily. The maintenance dose should be the lowest dose which keeps the patient symptom-free. Recommended doses are Adults . . . 0.5-1 mg twice daily. Children . . . 0.25-0.5 mg twice daily. When the advertisement was published, AstraZeneca's budesonide product was not approved for any use in the United States and was approved for only twice-daily use in Europe. Because it is undisputed that the asserted method claims cover the use of budesonide solution, the only question before the district court was whether the advertisement disclosed administering that solution in a continuing regimen at a frequency of not more than once per day as recited in the claims. The district court found that the advertisement does not anticipate the asserted method claims, finding persuasive the explanation of AstraZeneca's expert, Dr. Bradley Chipps, that the advertisement does not explicitly or inherently disclose once-daily dosing because the advertisement was published before we had any information or historical perspective that once a day therapy worked for anyone. Opinion at 596. The district court reached that conclusion with the understanding of Dr. Chipps, who also testified that, if made today, the statement [t]he maintenance dose should be the lowest dose which keeps the patient symptom-free would be equivalent to the downward-titration language included in the proposed label that AstraZeneca claimed would induce infringement of the asserted method claims. Prelim. Inj. Hr'g Tr. 186, May 4, 2009. On appeal, Apotex asserts that if the language in the Thorax advertisement would today suggest to those in the art the possibility of administering the drug once daily, it would also have suggested this possibility when the advertisement was published, regardless of whether anyone had proven that the drug could be effective when administered once per day. Apotex argues that in concluding otherwise the district court improperly imposed a temporal limitation on the anticipation inquiry, violating the oft-repeated axiom that which would literally infringe if later in time anticipates if earlier. AstraZeneca responds that because the drug was only approved for twice-daily use and was not known to be safe or effective when administered once daily, there is nothing to show that one of skill in the art at the time the patent application was filed would have understood the advertisement to disclose once-daily dosing. AstraZeneca thus argues that the Thorax advertisement was not enabling and for that reason cannot be considered anticipatory. In any event, AstraZeneca argues that the reference simply does not disclose once-daily dosing. Anticipation is a question of fact, Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075, 1082 (Fed.Cir.2008) (citation omitted), that must be established at trial by clear and convincing evidence, Purdue Pharma L.P. v. Boehringer Ingelheim GmbH, 237 F.3d 1359, 1365 (Fed.Cir.2001). This court reviews for clear error the district court's determination that AstraZeneca has demonstrated that the asserted method claims will likely survive the validity challenge posed by the Thorax advertisement. See Amazon.com, 239 F.3d at 1350. While the question is close, this court agrees with AstraZeneca that the district court correctly determined that AstraZeneca has demonstrated that the asserted method claims will likely withstand the validity challenge presented by the Thorax advertisement. In the context of anticipation, the question is not whether a prior art reference suggests the claimed subject matter as posited by Apotex. Rather, the dispositive question regarding anticipation [is] whether one skilled in the art would reasonably understand or infer from a [prior art reference] that every claim element is disclosed in that reference. In re Baxter Travenol Labs., 952 F.2d 388, 390 (Fed.Cir.1991). And although a reference must be enabling to be anticipatory, see Sanofi-Synthelabo, 550 F.3d at 1082, unlike enablement under § 112, a reference need not, as AstraZeneca suggests, demonstrate utility or efficacy to be enabling in the context of § 102, see In re Gleave, 560 F.3d 1331, 1335-36 (Fed.Cir. 2009) ([A] reference need disclose no independent use or utility to anticipate a claim under § 102.); Bristol-Myers Squibb Co. v. Ben Venue Labs., Inc., 246 F.3d 1368, 1379 (Fed.Cir.2001). As explained in Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318, 1325 (Fed.Cir. 2005), the reason for this distinction is that [§] 112 `provides that the specification must enable one skilled in the art to `use' the invention whereas [§] 102 makes no such requirement as to an anticipatory disclosure.' Id. (quoting In re Hafner, 56 C.C.P.A. 1424, 410 F.2d 1403, 1405 (CCPA 1969)). Apotex's argument that the Thorax advertisement is anticipatory because the advertisement and the proposed label are essentially the same ignores a key difference between the advertisement and the proposed label. As discussed in greater detail in the next section, depending on a patient's previous therapy, the proposed label recommends initially administering 0.25 mg of budesonide twice daily. The district court concluded that the proposed label would induce infringement because, absent instructions to the contrary, titrating down to the lowest effective dose from the recommended starting dose of 0.25 mg of budesonide twice daily would necessarily lead some users to take 0.25 mg of budesonide once daily as a maintenance dose, as there would be no way to properly administer less than 0.25 mg of the drug. By contrast, the Thorax advertisement explicitly discloses that such maintenance doses should be administered twice daily. Immediately after the advertisement warns that [t]he maintenance dose should be the lowest dose which keeps the patient symptom-free, the advertisement sets out recommended doses for adults and children: 0.5-1 mg twice daily for adults, and 0.25-0.5 mg twice daily for children. The most natural reading of this passage is that the recommended doses are recommended maintenance doses, which the advertisement explicitly states should be administered twice daily. Thus, although Dr. Chipps testified that the statement [t]he maintenance dose should be the lowest dose which keeps the patient symptom-free would, if made today, be equivalent to the downward-titration language included in the proposed label, the advertisementunlike the proposed labelclearly states how often a maintenance dose should be given: twice per day. Dr. Chipps confirmed that one of ordinary skill in the art would have understood the advertisement to disclose administering budesonide twice-daily, not once per day as argued by Apotex. He testified that there's nothing in [the Thorax advertisement] that talks about or alludes to once a day dosage, and noted that the advertisement instructs that the recommended starting and maintenance doses are to be administered twice daily. Prelim. Inj. Hr'g Tr. 144, May 4, 2009. Dr. Chipps opined that when the Thorax advertisement was published in 1994 a physician reading the dosing recommendations set forth in the advertisement would not have understood the dosing recommendations to teach once-daily dosing. Id. at 144. He explained that until AstraZeneca conducted clinical studies on its budesonide product in 1997 there was no evidence that administering budesonide once-daily would be safe and effective. Indeed, he noted that prior to 1997, the lowest dose of budesonide known to be effective was 0.25 mg taken twice a day. Id. at 147-48. Apotex presented no testimony or evidence to the contrary. After considering the reference and appreciating how that reference would have been understood by persons of ordinary skill in the art at that time, this court is not left with a definite and firm conviction that the district court clearly erred by concluding that at trial Apotex will likely not be able to demonstrate by clear and convincing evidence that the Thorax advertisement anticipates the asserted method claims. [2] Accordingly, the district court's determination is affirmed.