AstraZeneca loses in DNJ on patent claims protecting pulmicort
A pharmaceutically acceptable, micronized powder composition at least 98.5% by weight of which is pure budesonide or an ester, acetal or salt thereof, wherein the composition meets the criteria of sterility according to the US Pharmacopoeia [sic] 23/NF18, 1995, pages 1686-1690 and 1963-1975.'834 Patent col.11 11.48-52 (emphasis added). Claim 50 recites:
A pharmaceutically acceptable suspension consisting of a micronized powder composition at least 98.5% by weight of which is pure budesonide or an ester, acetal or salt thereof, suspended in an aqueous solution, wherein the suspension meets the criteria of sterility [*6] according to the US Pharmacopoeia [sic] 23/NF18, 1995, pages 1686-1690 and 1963-1975.'834 Patent col.13 11.54-60 (emphasis added). The dependent claims - claims 2 and 51 - include the additional limitation that 98.5% of the "micronized powder composition" is pure budesonide. '834 Patent col.11 ll.53-54 & col.13 11.61-63.
On appeal, the Federal Circuit reversed this Court's claim construction, construing the disputed term "micronized powder composition" to mean "finely divided dry particles" without requiring any particular process for sterilizing the particles. AstraZeneca, 542 F. App'x at 976-78. In light of the broadened claim construction, much of the remand proceedings centered on what was known in the art regarding the five conventional sterilization techniques. Defendants contend [*7] that now that AstraZeneca successfully obtained a broader claim construction not limited to a particular process, the so-construed patent is vulnerable to invalidity challenges based upon a significantly greater selection of prior art. See Sandoz Br., Docket No. 908, at 1, 8 ("AstraZeneca paid a steep price for its victory in the Federal Circuit.").
"To antedate (or establish priority) of an invention, a party must show either an earlier reduction to practice, or an earlier conception followed by a diligent reduction to practice." See Purdue Pharma L.P. v. Boehringer Ingelheim GmbH, 237 F.3d 1359, 1365 (Fed. Cir. 2001) (citation omitted). "In order to establish an actual reduction to practice, the inventor must prove that: (1) he constructed an embodiment or performed a process that met all the limitations of the interference count; and (2) he determined that the invention would work for its intended purpose. . . . The inventor must also 'contemporaneously appreciate that the embodiment worked and that it met all the limitations of the interference count." Henkel Corp. v. Procter & Gamble Co., 560 F.3d 1286, 1289 (Fed. Cir. 2009) (citation omitted); see also Purdue Pharma, 237 F.3d at 1365-66. The patentee bears the burden of producing evidence supporting an earlier invention date but the burden of proof remains on the defendant "to establish by clear and convincing evidence that the patentee's invention date does not precede the date of the ostensible prior art reference." Power Integrations, Inc. v. Fairchild Semiconductor Int'l, Inc., 585 F. Supp. 2d 568, 575-76 (D. Del. 2008) (citing Spectralytics, 576 F. Supp. 2d at 1045).5 AstraZeneca points to laboratory-reports, dated March 1997, demonstrating inter alia that heating the substance for 60 minutes at 110 ° C would result in more than a 7 log reduction in [*13] Bacillus subtilis spores. See PTX 1034 at 1335867; PTX 1527. Redacted versions of these laboratory reports were submitted with AstraZeneca's Rule 131 Declaration. PTX 5A. Dr. George Zhanel, an expert for AstraZeneca, and Dr. Cheryl Larrivee-Elkins, one of the named inventors on the '834 Patent, testified that a six or seven log reduction was the "standard" used to define the goal of a sterilizing process because it indicates a 1/1 million sterility assurance level. See 2012 Trial Tr. 615:2-11; id. at 4213:9-16. Dr. Zhanel further testified that a POSA would understand from the laboratory data that this experiment would result in a sterile product as it demonstrates rapid spore reduction. Id. at 4276:9-4277:16. Although Defendants' expert, Dr. Scott Sutton, testified that this data only demonstrates spore reduction and not a sterilized product, he acknowledged that he was the "wrong person to ask" how the spore reduction translated into sterility. Id. at 2463:14-18, 2465:20-23. However, while the conclusion expressed in the documents was that heating for 60 minutes at 110 ° C "will give" more than a 7 log reduction, PTX 1034 clearly demonstrates that the samples were not actually heated at that time and [*14] temperature. PTX 1034 at 1335866-67; cf. Purdue Pharma, 237 F.3d at 1365 ("To prove actual reduction to practice, 'an inventor must establish that he actually prepared the composition . . . ." (citing Estee Lauder Inc. v. L'Oreal, S.A., 129 F.3d 588, 592 (Fed. Cir. 1997))). Similarly, PTX 1527 provides no information regarding sterility of the heat-treated samples, and the testing conducted was not intended to even address sterility. See PTX 1527 at 1339829.
A patent is invalid as obvious if the differences between the claimed invention and prior art are such that the invention as a whole would have been obvious to a person of ordinary skill in the art at the time the invention was made. Sciele Pharma, 684 F.3d at 1259 (quoting 35 U.S.C. § 103(a)). Whether a patent claim is obvious is a question of law based on four underlying facts: 1) the scope and content of the prior art; (2) the level of ordinary skill in the pertinent art; (3) the differences between the prior art and the claims at issue; and (4) such secondary considerations as commercial success, long-felt but unsolved need, and the failure of others. Id. (quoting Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966)); see also KSR Int'l. Co. v. Teleflex, Inc., 550 U.S. 398, 406 (2007).
AstraZeneca's response to Defendants' evidence actually serves to confirm this Court's obviousness finding. Importantly, AstraZeneca does not dispute that sterile filtration was a known sterilization process. Nor does it dispute that a POSA had a reasonable expectation of successfully performing [*59] a sterile filtration of a budesonide solution. Trial Tr. 2284:16-20 (Akers) ("Q. And I think we agreed the. sterilization step, you have no problem with that, the skilled person could reasonably expect success in performing a sterile filtration of the budesonide solution, correct? A. They could reasonably expect success . . . ."). And their own witness, Dr. Akers, agreed that the steps in the 1994 FDA Inspection Guide were typical in 1997. See PTX 2110 at 54 ("The preparation of sterile solids typically includes a sterile filtration, followed by crystallization, filtration, washing, drying, milling, and blending, all of which are carried out under sterile conditions.");
Yet, as the Federal Circuit has ruled, the patent is not limited to a process (a practical way), but rather it covers a product. The fact that AstraZeneca admitted to the PTO that there existed a (arguably) less practical way to make the product in and of itself, it seems, should end the obviousness analysis. Notably, in Orthopedic Equipment Co. v. United States, 702 F.2d 1005 (Fed. Cir. 1983), the Federal Circuit recognized that while a POSA may not combine two [*78] prior art apparatuses for "economic feasibility" reasons, that decision is not relevant to nonobviousness. 702 F.2d at 1013 ("In other words, the fact that the two disclosed apparatus would not be combined by businessmen for economic reasons is not the same as saying that it could not be done because skilled persons in the art felt that there was some technological incompatibility that prevented their combination. Only the latter fact is telling on the issue of nonobviousness."). Similarly, while a drug manufacturing company may not have ultimately utilized sterile filtration in combination with aseptic processing to manufacture sterilized budesonide in bulk due to the associated high costs of maintaining an aseptic environment at that scale, that is not to say that a POSA would not be motivated to employ these well-known sterilization processes in a laboratory with a reasonable expectation of successfully preparing the claimed sterilized budesonide compositions.
For the reasons set forth above, the evidence clearly and convincingly demonstrates that a POSA would have had a reasonable expectation of successfully preparing the claimed sterile budesonide compositions (the powder set forth in claims 1 and 2, and the suspensions set forth in claims 50 and 51) using four of the five conventional sterilization techniques (i.e., sterile filtration/crystallization, moist heat, EO, and irradiation). Moreover, there is insufficient evidence of secondary considerations of nonobviousness. See Wyers v. Master Lock Co., 616 F.3d 1231, 1246 (Fed. Cir. 2010) ("[S]econdary considerations of nonobviousness . . . simply cannot overcome a strong prima facie case of obviousness."). As such, the asserted claims are invalid as obvious.