Opinion ID: 2620291
Heading Depth: 2
Heading Rank: 3

Heading: ’603 Patent Claim Invalidity

Text: The district court found the asserted claims of the ’603 Patent invalid as obvious and as anticipated. As for obviousness, the district court concluded that the ’603 patent’s “essential teaching” is “once-daily dosing of nebulized budesonide” and that a person of ordinary skill in the art would have been motivated to arrive at this “obvious conclusion.” Opinion at . The obviousness analysis involves four factual inquiries: (1) “‘the scope and content of the prior art,’” (2) the “‘differences between the prior art and the claims at issue,’” (3) “‘the level of ordinary skill in the pertinent art,’” and (4) “‘secondary considerations’” of nonobviousness. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 406 (2007) (quoting Graham v. John Deere Co. of Kan. City, 383 U.S. 1, 17–18 (1966)). “One of the ways in which a patent’s subject matter can be proved obvious is by noting 14 ASTRAZENECA LP v. BREATH LIMITED that there existed at the time of invention a known problem for which there was an obvious solution encompassed by the patent’s claims.” Id. at 419–20. “[I]n many cases a person of ordinary skill will be able to fit the teachings of multiple patents together like pieces of a puzzle.” Id. at 420. “A person of ordinary skill is also a person of ordinary creativity, not an automaton.” Id. at 421. When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103. Id. at 421. The district court found that the prior art included numerous studies, which “taught the safety and efficacy of once-daily inhaled budesonide” (“once-daily studies”), including once-daily treatment of children. Id. at . Further, the district court found that practitioners were taught to use a “stepwise” approach to dosing, wherein the practitioner would attempt to titrate the drug dose down to the lowest possible dose—a once-a-day dose. Id. at . Relatedly, the district court concluded that it was a known problem that the dosing frequency of young children with asthma created “issues of compliance and convenience.” Id. at –21. AstraZeneca notes that none of the once-daily studies teaches use of a nebulizer to administer the drug. Id. Instead, the once-daily studies taught use of two other delivery devices: MDI and PDI. MDI devices use a canister filled with the drug, which when pressed by the user, propels the drug into a gaseous ASTRAZENECA LP v. BREATH LIMITED 15 solution inhaled by the patient. Id. MDIs are difficult for patients to use because proper inhalation of the gaseous solution requires considerable coordination. Id. DPI devices are similar, except that the user’s own inhalation is used to propel the drug, which is a problem for small children. Id. Nebulizers create, without any effort from the patient, a fine mist of the drug. Id. The patient merely breaths and inhales the mist. Nebulizers are inefficient because much of the drug is lost to the air or ingested by the patient. Id. The district court found that a publication by Brattsand & Selroos teaches that budesonide can be delivered via several different mechanisms, including nebulization, and though mistaken as to the correct mechanism, teaches that budesonide delivered to the lungs exhibits a “depot effect” where the drug continues to have an effect for a significant period after it is administered. Id. at –15. According to the district court, references such as Jackson and McCarthy further teach that the delivery method of budesonide does not impact its clinical effectiveness. Id. at –18. The district court also observed that the prior art also teaches that nebulizers were the “most practical delivery device for certain patients like young children.” Id. at . The district court also made the following findings as to references by Jackson, McCarthy, and Möller. Though not in connection with once-daily dosing, Jackson specifically teaches use of nebulized budesonide on infants and children under three-years old. Id. McCarthy and Möller similarly teach use of inhaled budesonide once daily in the treatment of children of various age ranges, including 5 to 13, 7 to 13, as well as “small children” and “infants.” Id. at 26. We can find no clear error with respect to these factual findings. With respect to the differences between the prior art and the claimed invention, AstraZeneca contends that 16 ASTRAZENECA LP v. BREATH LIMITED the ’603 Patent fills two gaps existing in the prior art, neither of which would have been obvious: (1) use of a once-daily nebulizer budesonide treatment and (2) a oncedaily treatment of children. The district court found that the once-daily studies demonstrate the safety and efficacy generally of oncedaily inhaled budesonide. Opinion at , 15–16, 20. The district court also found that though Brattsand & Selroos incorrectly identify the location of the budesonide binding site, and thus incorrectly describe the budesonide depot mechanism, a person of ordinary skill in the art at the time of the invention nonetheless would have expected budesonide to exhibit the depot effect, which is an inherent property of the drug regardless of how it is delivered to the lung. Opinion at . This depot effect makes the drug attractive to once-daily dosing. Further, the district court found that Jackson and McCarthy teach that the delivery method of the budesonide does not impact its effectiveness. Opinion at –18. We agree with these findings and see no clear error by the district court. We also agree with the district court that the “compliance and convenience” factors, as well as the recognized stepwise approach to dosing suggest that once-daily dosing would have been preferred, especially with respect to young children. Moreover, the evidence established a reasonable expectation of success for once-daily treatment of children. The district court found testimony of Appellees’ expert, Dr. Barnes, credible with respect to the fact that “that a person of ordinary skill in the art would not have any concerns about using nebulized budesonide once daily in children under the age of five, because the principles for treating this patient group and for treating older children and adults are the same.” Opinion at . We can find no clear error in this finding, particularly in light of the numerous studies—such as Jackson, Möller, and McCarASTRAZENECA LP v. BREATH LIMITED 17 thy—each teaching treatment of children (from infants to age 13) with inhaled budesonide. Id. 1 Furthermore, the district court found, and the parties agreed, that a known problem existed at the time of the invention: “significant difficulty in the treatment of young children, including infants, who suffer from respiratory disease.” Opinion at . Because children lack coordination and the ability to take strong breaths, which are required for MDI and PDI delivery but not for nebulizers, nebulizers would have been an obvious way to overcome the problem of finding an effective delivery mechanism to treat young patients. Moreover, the district court’s factual findings establish a reasonable expectation of success for that treatment. The once-daily studies demonstrated the effectiveness of once-daily treatment with budesonide, including the treatment of young children. Use of nebulizers to administer budesonide was known, and based on the teachings of Jackson and McCarthy, those of skill in the art would not have expected differences in the budesonide delivery method to impact efficacy. With respect to secondary considerations, AstraZeneca first points to alleged industry skepticism, noting inventor testimony that AstraZeneca did not believe oncedaily dosing would be effective, as evidenced by AstraZeneca’s decision to add not one, but two clinical studies 1 The rebuttal evidence cited by AstraZeneca merely established that for young children asthma is particularly dangerous and difficult to diagnose. The evidence does not show that a person of skill in the art would believe that the principles making once-daily budesonide treatment safe and effective for adults differ from those for young children. 18 ASTRAZENECA LP v. BREATH LIMITED with respect to once-daily dosing. In addition to a study concerning twice-daily dosing, AstraZeneca added studies for once-daily dosing and a study looking both at oncedaily and twice-daily dosing. The district court found, and we agree, that this simply is evidence of corporate prudence based on AstraZeneca’s own misgivings rather than industry skepticism. AstraZeneca also argues long-felt, unmet need for once-daily dosing of budesonide via a nebulizer, noting that Pulmicort Respules® had been available for twicedaily dosing since 1990, but the efficacy of once-daily dosing of nebulized budesonide was not investigated prior to 1997. See Opinion at –12. That fact, alone, is inconclusive and insufficient in the circumstances of this case to support the argument of non-obviousness. This court identifies no clear error in any underlying factual determinations of the district court, and finds that those facts establish by clear and convincing evidence that the asserted claims of the ’603 Patent are obvious. This court, therefore, affirms the district court’s obviousness finding. Given this court’s conclusion on obviousness, we need not reach the issue of anticipation.