Last year marked the fifth anniversary of the Supreme Court landmark decision in KSR v. Teleflex (April 30, 2007), when our nation’s highest court addressed the obviousness of patents under 35 U.S.C. § 103 for the first time since Graham v. John Deere in 1966. But the patent-at-issue in KSR was mechanical. Patent holders in the chemical arts were wondering whether (more akin to hoping?) KSR’s loosening of the obviousness analysis might have less impact on chemical / pharmaceutical inventions, as opposed to mechanical inventions, because of inherent unpredictability in the art of the former. As we enter 2013, we think this is a good time to review Federal Circuit decisions from the last twelve months to discern trends and patterns in the post-KSR obviousness analysis of chemical patents.
A few trends were readily apparent in 2012. First, pharmaceutical patent holders in litigation fared well – in a series of cases, the Federal Circuit rejected obviousness attacks in pharmaceutical patent challenges on appeal from the district courts. Second, patent holders appealing decisions from the Board of Patent Appeals and Interferences (whether it be an original application, a reexamination, or a reissue) fared poorly – the Federal Circuit affirmed several Board decisions finding chemical patent claims obvious. While these trends are not surprising, a third more subtle trend suggests chemical patents in district court litigation may be less susceptible to invalidation for obviousness post-KSR. In 2012, when the Federal Circuit reversed the obviousness decision below on a chemical patent, those reversals favored non-obviousness three to one.
Our review lends itself to dividing the 2012 Federal Circuit obviousness decisions in chemical cases in three different categories: appeals from i) pharmaceutical litigation, ii) PTO Board decisions, and iii) non-pharmaceutical litigation over chemical patents. What follows is our review of appeals from pharmaceutical litigation. Part II of the article will focus on PTO Board decisions and appeals from non-pharmaceutical litigation relating to chemical patents.
One of the biggest cases decided in 2012 was one of the last decided – Astrazeneca v. Aurobindo (In re Rosuvastatin Calcium Patent Litigation), 2010-1460, 2012 U.S. App. LEXIS 25694 (Fed. Cir. Dec. 14, 2012) (the Crestor litigation). If one takes nothing more from Aurobindo concerning obviousness, know that it reaffirms the Federal Circuit’s pre-KSR decision in Yamanouchi Pharm. Co. v. Danbury Pharmacal, Inc. (Fed. Cir. 2000), finding a patent non-obvious where “an ordinary … chemist” would not have expected the specific chemical structure to have the “most desirable combination of … properties.” In Aurobindo, the Federal Circuit compared the closest prior art, referred to as Sandoz Compound 1b, which has two –CH3 groups on the amino side chain, with the patented rosuvastatin, which instead has one methyl group and one –SO2CH3 group. Defendants argued that Sandoz Compound 1b would be a good “lead compound” for further research and that the change to rosuvastatin would have been obvious because it would make the 1b compound more hydrophilic, which would be better for the liver. Plaintiffs countered by arguing that 1b would not be a good lead compound because of unexpected increased toxicity and there was no “reasonable expectation of success.” Plaintiffs also highlighted the unpredictability of statin development and argued no reference or combination of references suggested that rosuvastatin, which was a “previously unknown molecule,” would have its advantageous properties.
The Federal Circuit panel (opinion by Judge Newman) agreed with the Plaintiffs, citing KSR (be aware of hindsight analysis) and its pre-KSR decision in Yamanouchi. It concluded that Defendants’ “obvious to try” argument was negated by the general skepticism in the field and that the prior art taught a different preference than that chosen by the patentee. The Federal Circuit concluded by reiterating its holding in Takeda Chem. Indus., Ltd. v. Alphapharm Pty., 492 F.3d 1350 (Fed. Cir. 2007) that, in cases involving new chemical compounds, it is still necessary to identify a reason that would have led a chemist to modify a known compound in a particular manner.
Aurobindo marks a departure from, and spells relief to pharmaceutical patent holders in comparison to Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348 (Fed. Cir. 2007), a pre-KSR obviousness decision by the Federal Circuit, which was denied rehearing post-KSR. In Pfizer, the Federal Circuit held “obviousness cannot be avoided simply by a showing of some degree of unpredictability in the art so long as there was a reasonable probability of success.” However, the Pfizer court did not clarify when a solution is unpredictable yet its success reasonably probable. Pfizer may also be distinguishable from Aurobindo in that the question of obviousness turned on the selection of a salt species, as opposed to the composition of the parent compound itself. Judge Newman dissented from the denial of the rehearing en banc in Pfizer, so she likely would have decided that case differently than the majority.
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Aripiprazole is the active ingredient in Otsuka’s antipsychotic drug Abilify. Several generic drug manufacturers submitted ANDA filings, and in the ensuing litigation, each conceded infringement but asserted that the claims in the patent-at-issue were invalid for obviousness and obviousness-type double patenting. Otsuka Pharma. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280 (Fed. Cir. 2012). The defendants argued that aripiprazole would have been obvious over three prior art carbostryil derivative compounds, but the district court disagreed and found in favor of Otsuka.
The Federal Circuit first addressed whether a chemist would have selected one of three asserted prior art compounds as a lead, i.e., whether the compound is “a natural choice for further development efforts.” It cautioned that “mere structural similarity between a prior art compound and the claimed compound does not inform the lead compound selection.” It next addressed whether the prior art would have provided one skilled in the art with a reason to modify a lead compound in order to come up with the claimed compound, and to have a reasonable expectation of success in doing so. The Court distinguished Pfizer v. Apotex because, in that case, the prior art reference provided sufficient motivation to narrow the prior art genus and also predicted the results. It found that there was no such analogous showing in this case and did not even address secondary considerations of non-obviousness because it held that a prima facie case of obviousness had not been made. The Federal Circuit affirmed the district court’s “careful” obviousness analysis, stating that Defendants’ obviousness case was “a poster child for impermissible hindsight reasoning.”
In Santarus, Inc. v. Par Pharmaceutical, Inc., 694 F.3d 1344 (Fed. Cir. 2012), the patents-at-issuewere directed to benzimidazole proton pump inhibitors (PPI) used to inhibit gastric acid secretion. Several benzimidazoles had previously been approved by the FDA for PPI use, but each needed to have an acid-resistant enteric coating. The Santarus products (and the patents it exclusively licensed) do not have an enteric coating so the PPI is absorbed directly from the stomach into the bloodstream.
The Federal Circuit panel upheld the district court’s decision that several asserted claims were invalid as obvious for each claim to which the patentee’s own ‘737 patent was prior art (due to breaks in the chain of priority). Judge Newman disagreed, noting in her dissent that the prior art references explicitly teach away from the claimed inventions, citing to KSR’s caution against “the distortion caused by hindsight bias” and “arguments reliant upon ex post reasoning” in determining obviousness.
For those claims to which the ‘737 patent was not prior art, however, the panel reversed the district court’s finding of obviousness for claims directed to conventional oral dosage forms because it found that the prior art taught away from the claimed invention. Notably, in analyzing whether the reference “teaches away” from the claimed invention, the court relied exclusively upon pre-KSR case law.
In Alcon Research, Ltd. v. Apotex Inc., 687 F.3d 1362 (Fed. Cir. 2012), the Federal Circuit reversed the district court in part, and affirmed in part. Judge Young in the Southern District of Indiana held, after a bench trial, that claims 1-8 of Alcon’s patent directed to a method for treating allergic eye disease would not have been obvious over the prior art. The Federal Circuit disagreed with respect to claims 1-3 and 5-7, finding those claims obvious because the prior art Kamei reference disclosed animal test results for olopatadine concentrations that overlapped with the ranges in the patent claims directed to human application. The Federal Circuit’s reversal and determination of obviousness was based on the district court’s error in finding that “a person of skill in the art would not have been motivated to use the olopatadine concentration disclosed in Kamei in human eyes,” despite the district court’s factual finding that “animal tests, including guinea pig models, are predictive of a compound’s antihistaminic activity and its topical ocular availability in humans.” It cited KSR for the proposition that it is error to look “only to the problem the patentee was trying to solve.”
For claims 4 and 8, however, the appellate court agreed with the lower court that the claims were not invalid. It reasoned that these claims were limited to using formulations with an olopatadine concentration of about 0.1% w/v, and Kamei only tested formulations with concentrations up to 0.01%. Essentially, the Federal Circuit concluded that claims 4 and 8 would not have been obvious to try (“a person of ordinary skill in the art would have been concerned that olopatadine might be biphasic at this increased concentration, and thus would not have tried a formulation with ten times more olopatadine than the highest dosage used in Kamei.”). It also concluded that secondary considerations, particularly commercial success, supported the holding that claims 4 and 8 were not obvious.
Extended-Release Cyclobenzaprine Litigation
In Eurand, Inc. v. Mylan Pharms., Inc. (In re Cyclobenzaprine Hydrochloride Extended-Release Capsule Patent Litig.), 676 F.3d 1063 (Fed. Cir. 2012), the Federal Circuit reversed and vacated the district court’s judgment of invalidity for obviousness of two patents directed to muscle relaxants, and marketed by Celphalon under the brand name Amrix. The panel based its holding on the district court’s erroneous “legal conclusion that bioequivalence alone was sufficient to render the claims at issue obvious[.]” The Federal Circuit found that the district court placed undue weight on bioequivalence and, as a result, misinterpreted the prior art, further noting that it should not be the patentee’s burden to disprove a district court’s initial obviousness finding.
Notably, the Court stated:
Where a skilled artisan merely pursues “known options” from “a finite number of identified, predictable solutions,” the resulting invention is obvious under Section 103. KSR, 550 U.S. at 421. Where, however, a defendant urges an obviousness finding by “merely throw[ing] metaphorical darts at a board” in hopes of arriving at a successful result, but “the prior art gave either no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful,” courts should reject “hindsight claims of obviousness.” In re Kubin, 561 F.3d 1351, 1359 (Fed. Cir. 2009) (quoting In re O’Farrell, 853 F.2d 894, 903 (Fed. Cir. 1988)).
So, if you are keeping score, the pioneer drug companies prevailed, at least in part, in all five Federal Circuit decisions in 2012 addressing obviousness. Three cases resulted in complete victories (two affirming the district court below, and one reversing) and the other two cases resulted in partial victories (one reversing the district court’s obviousness holding for some of the claims, and one affirming the district court’s non-obviousness holding for some of the claims).
 In the interest of full disclosure, note that one of our partners, Mary Bourke, is one of the attorneys representing Astrazeneca in this case.
 Similarly, in Eli Lilly and Co. v. Teva Parenteral Medicines, Inc., 2011-1561, the Court addressed obviousness-type double patenting and affirmed the district court’s finding that the claims were not invalid: “In the chemical context, we have held that an analysis of obviousness-type double patenting ‘requires identifying some reason that would have led a chemist to modify the earlier compound to make the later compound with a reasonable expectation of success.’” It agreed with the district court that, regarding a complicated compound (such as the one claimed in the Eli Lilly patent) which provided many opportunities for modification, substituting a phenyl group into the aryl position was not the “one, among all the possibilities, that would have been successfully pursued.”
 For those claims directed to suspensions of buffered non-enteric coated omeprazole, however, it found that the prior art did not provide “clear discouragement” as required by Federal Circuit precedent. Those claims were held invalid.
About the Authors
Barry Herman is an intellectual property litigation partner at Womble Carlyle Sandridge & Rice, LLP. Barry holds a Bachelor of Science degree in chemical engineering from Lehigh University, and a Juris Doctor from the University of Maryland School of Law. Barry represents both domestic and foreign clients in a wide range of intellectual property matters, with an emphasis on patent litigation in district courts and before the International Trade Commission. He can be contacted by email at email@example.com or by phone (410) 545-5830.
Jim Lennon is a registered patent attorney and litigator at Womble Carlyle Sandridge & Rice, LLP. Jim holds a Bachelor of Science degree in Geology from the University of Delaware, and a Juris Doctor from the University of North Carolina School of Law. Jim is an advocate for enforcers and challengers of patent rights in all patent disputes venues, working all levers of the patent system to his clients’ advantage. Jim can be contacted by email at JLennon@wcsr.com or by phone at (302) 252-4326.
NOTE: The views herein expressed are solely those of the authors and are not necessarily the views of Womble Carlyle or its clients.