By Andrew Williams --
Last week, the Federal Circuit partially overturned the U.S. District Court for the District of Delaware's decision in Santarus, Inc. v. Par Pharmaceutical, Inc., thereby allowing Santarus to keep Par's generic version of Zegerid® off the market until the expiration of the Orange Book-listed patents. Judge Newman provided a separate opinion, also finding that Santarus should have been successful, but disagreeing with the majority per curiam opinion on the issues of what is required for written description of a negative claim limitation, whether the subject matter in a parent patent can serve as prior art to a chain of continuation-in-part applications, and whether a claimed invention can be considered obvious in view of overwhelming evidence of unexpected results and skepticism in the field.
The technology at issue in this case involved specialized formulations of benzimidazole proton pump inhibitors ("PPIs"), such as omeprazole or lansoprazole. This class of compounds is able to inhibit gastric acid secretion to prevent and treat stomach acid-related diseases and disorders. Even though these PPIs block stomach acid production, they are extremely sensitive to this same acid. Therefore, the prior art FDA-approved formulations included an enteric coating to protect the active ingredient. Dr. Phillips, at the University of Missouri, figured out how to formulate these drugs without the enteric coating by including a buffering agent that allowed the PPIs to be directly absorbed from the stomach into the blood stream. This had numerous advantages, including rapid and consistent bioavailability, increased effectiveness, and ease of administration (thereby assisting patient compliance). Dr. Phillips filed a first provisional on January 4, 1996, to which the first patent, U.S. Patent No. 5,840,737 ("the '737 patent"), claimed priority. All of the patents at issue in this case were either continuations or continuations-in-part in a chain that stretched back to the '737 patent. The patents-in-suit included U.S. Patent Nos. 6,489,346 ("the '346 patent"), 6,645,988 ("the '988 patent"), 6,699,885 ("the '885 patent"), 6,780,882 ("the '882 patent"), and 7,399,772 ("the '772 patent").
The present action was initiated after Par filed an ANDA to market the same formulation as the Zegerid® PPI. In response to Santarus' claims of infringement of selected claims of the patents-in-suit, Par alleged that it did not infringe, and asserted that the claims at issue were unenforceable, as well as invalid for either a lack of written description or as being obvious over the prior art. The Delaware Court found that the claims were infringed, and that they were not unenforceable, but that some of the claims of the '772 patent were invalid as failing the written description requirement, and that all claims were invalid as obvious. Both parties appealed the rulings adverse to it, but Par did not challenge the finding of infringement.
As an initial matter, the Federal Circuit affirmed the lower court's finding that the applicant did not commit inequitable conduct. Par had alleged that Dr. Phillips had intentionally withheld information during the prosecution of the parent application, and only submitted it during the prosecution of subsequent applications. Dr. Phillips claimed that he was not aware that he needed to submit information related to the experimental administration to patients. In addition, once the University's patent counsel became aware of the information, he submitted it in an Information Disclosure Statement. The lower court found that Dr. Phillips's explanation "strained credibility," but that there was insufficient evidence to establish by clear and convincing evidence that there was an affirmative intent to deceive. On appeal, Par stressed the "strained credibility" comment, but the entire panel agreed that the lower court's decision was in accord with Therasense. This determination is good news for pharmaceutical companies that in-license technology from Universities. With a different outcome, entire patent portfolios could have been jeopardized based solely on the misconceptions of inventors who are not always aware of the intricacies of patent law.
The next issue related to the adequacy of disclosure involving certain claims of the '772 patent that had the negative limitation "wherein the composition contains no sucralfate." This limitation was apparently added during the prosecution of the application, citing to the specification's highlighting that sucralfate and other compounds have certain disadvantages. The lower court, majority, and concurrence all took different views of what is required to support a negative limitation. On the one hand, the District Court held that the negative limitation could only be added if the specification demonstrated that sucralfate was contraindicated. The lower court concluded that, because the Phillips' composition was only described as advantageous in the specification, the negative limitation could not satisfy the written description requirement. The majority took a more lenient approach, pointing out that "[n]egative claim limitations are adequately supported when the specification describes a reason to exclude the relevant limitation." Because those skilled in the art would understand that the disadvantages of including sucralfate could be avoided by the Phillips formulation, the written description was satisfied. Furthermore, because the originally filed application contained the same disclosure related to sucralfate, these claims were entitled to claim priority back to the '737 patent (which is an important consideration for the obviousness analysis).
Judge Newman agreed that the negative limitation had adequate written description support, and that these claims were entitled to the priority claim, but she complained that the majority opinion unnecessarily created a new requirement that a specification "describe a reason" for a claim limitation. In justifying her criticism, she pointed out that applicants routinely amend claims during prosecution in response to prior art cited by the Patent Office. Moreover, she pointed out that data may be generated during the application process that may necessitate claim amendments that were not necessarily appreciated when the application was filed. By requiring a reason in the specification for a negative limitation, she warned, a patent applicant may no longer be able to sufficiently narrow an application to get around the prior art. Ultimately, she concluded, the Court's new requirement adds uncertainty, which will be to the detriment of commerce.
Obviousness – '737 patent as prior art
The more interesting issue relating to sufficiency of disclosure involved the use of the ultimate parent, the '737 patent, as prior art against a subset of the asserted claims. The patents at issue were all continuations and continuations-in-part that reached back to the '737 patent. The District Court had made a priority determination for all of the claims, and because it determined that a subset of the claims could not claim priority to the '737 patent, that patent could be cited as prior art. Interestingly, except for the sucralfate claims mentioned above, Santarus did not challenge the lower court's priority determination as to any of the claims.
The Federal Circuit overturned the obviousness determination with regard to the sucralfate negative limitation claims. However, because the '737 patent disclosed all of the limitations of the other asserted claims, the Court upheld the obviousness determination. The dissent pointed out that the problem with this decision was that, if the '737 patent did, in fact, contain all of these limitations, why were these patents unable to claim priority back to the same disclosure. In fact, Judge Newman appears to take the position that subject matter common to a patent and a priority document can never be used to invalidate a patent claim.
Santarus had made three arguments as to why the '737 patent failed to disclose the claimed subject matter. In the first two arguments, it alleged that the '737 patent failed to disclose non-enteric coated PPIs and buffer within the claimed ratios, and failed to disclose that the buffering agent be sodium bicarbonate "in an amount from about 1000 mg to about 2000 mg." For both of these arguments, the majority went to great effort to point out how these ratios or ranges overlap ranges disclosed in the '737 patent. However, the majority opinion did not explain why one skilled in the art would have selected the particular claimed range, or would have had any expectation that such a range would work. Presumably, therefore, the overlap was so great that such a determination was unnecessary. If this was the case, though, it is unclear why the '737 patent did not anticipate the claims at issue rather than just render them obvious. Santarus' final argument was that the '737 patent did not recite the specific blood serum concentrations of PPI that were recited in some of the claims. The Court pointed out that such concentrations were inherent properties of the '737 patent, and therefore their inclusion in the claim could not otherwise make an invalid claim valid. Again, the problem is that the Court was undertaking an obviousness determination, and as such, inherency should not be a factor. Instead, the analysis should focus on why one skilled in the art would have selected the particular concentrations to arrive at the claimed blood serum concentrations. Of course, if the '737 patent "anticipated" the claims, than it is unquestionable that one could not simply claim the inherent properties of carrying out the disclosure.
Judge Newman appears to have a valid point that the subject matter of the '737 patent should not be used as prior art against the claims at issue, especially in view of the fact that the obviousness determination was in view of only the single reference, and that reference appears to anticipate the claims more than render them obvious. Of course, if the '737 patent "anticipated" the claims at issue, then it must have supported the claims in the first place. As unsatisfactory as it is, the answer probably lies in the fact that Santarus did not challenge the lower court's priority determination. It would be very interesting to see if the majority opinion would have been different would Santarus have done so.
Obviousness – '737 patent not prior art
Finally, the lower court had held that the remaining asserted claims were invalid as obvious in view of two references, Pilbrant and Lammers. The majority overturned this determination with regard to conventional oral dosage forms, such as tablets, capsules, or granules with non-enteric coated PPIs, because it found that Pilbrant taught away from formulating omeprazole according to the claims with regard to these forms. However, the majority did not accept Santarus' assertion that Pilbrant taught away from all non-enteric coated omeprazole formulations. As a result, the Court upheld the obviousness determination with regard to these claims.
The dissent, again, would have overturned the invalidity determination with regard to all of the claims. As Judge Newman pointed out, the majority opinion failed to take into account the entirety of the Pilbrant teaching. Apparently, when read properly, Pilbrant actually taught away from using omeprazole without the enteric coating. Moreover, according to Judge Newman, the majority erred by only focusing on these two references, and failed to take into account the state of the art, in which every patent or publication stated that PPI must be enteric coated. In fact, there was apparently much skepticism in the art that the Phillips formulation would even work. As such, Judge Newman accused the majority of using hindsight reasoning. Finally, Zegerid® had sales of over $100 million in 2008, demonstrating commercial success, which the dissent pointed out can be highly probative of the non-obviousness.
Santarus, Inc. v. Par
Pharmaceutical, Inc. (Fed. Cir. 2012)
Panel: Chief Judge Rader and Circuit Judges Newman and Moore
Opinion for the court Per Curiam; opinion concurring in part and dissenting in part by Circuit Judge Newman