Unigene Labs. and Upsher-Smith Labs v. Apotex (Fed. Cir. 2011)
One critical reading of this case is that the Federal Circuit intends to continue to take steps to ensure that important chemical formulation patents are considered valid. In particular, the court explicitly aligns the obviousness analysis of claims for formulations of known compounds with that of claims for novel compounds. In doing so, the court seemingly ignores KSR’s negative outlook on combination claims. The case is also important in the way that the (unclaimed) purpose of a particular element of a combination claim can be used to overcome an obviousness argument.
Background: Unigene’s reissued patent No. RE40,812 covers its Fortical calcitonin nasal spray. Unigene developed Fortical as a bioequivalent alternative to Novartis’s Miacalcin calcitonin nasal spray. Unigene relied on bioequivalence to the already approved formulation to speed its FDA approval process. The differences between the formulations are in the levels of non-pharmaceutically active components of the nasal spray.
In particular, the prior-art Miacalcin spray includes 2,200 I.U./mL of calcitonin and also sodium chloride, nitrogen, HCL, water, and benzalkonium chloride. Unigene’s Fortical contains the same amount of calcitonin, along with 20 mM citric acid, polysorbate 80, phenylethyl alcohol and benzyl alcohol. These contents in their required ratios are claimed in Unigene’s patent.
In 2006, generic manufacturer Apotex filed an abbreviated new drug agreement (ANDA) to begin importing a generic version of Unigene’s Fortical nasal spray before the patent’s expected expiration date. Because that filing constitutes prima facie patent infringement under 35 U.S.C. § 271(e)(2), Unigene sued for infringement.
On summary judgment, the district court dismissed Apotex’s obviousness defense — holding that, as a matter of law, the asserted claims would not have been obvious at the time of invention. 35 U.S.C. 103(a).
On appeal, the Federal Circuit affirmed and provided a further analysis of how the Supreme Court’s KSR decision applies (or does not apply) in the chemical arts.
Begin with a “lead compound” or “reference composition”: In most chemical-compound cases, the obviousness analysis begins with the closest prior art compound — termed a “lead compound.” In this type of composition claim, an ordinary approach is to begin with a “reference composition.” Here, that reference is the Miacalcin formulation. Here, there was a strong market demand to identify a bioequivalent composition that avoids the Miacalcin patent since a bioequivalent would have the best chance of receiving FDA approval.
Although the prior art would point one of ordinary skill in the art toward a particular starting point and provide motivation to develop a bioequivalent, these factors to not indicate which bioequivalent among an infinite number of possible formulations is the best.
Here, Unigen focused on its use of 20 mM of citric acid as a absorption enhancer and surfactant in Fortical. The prior art Miacalcin uses BZK for that function. A prior art reference showed experimental data that citric acid mixed with calcitonin in tablet form increased absorption. However, the court ruled that reference “would not cause a person of ordinary skill to replace BZK in Miacalcin with 20 mM of citric acid in the normal course of research and development[, and therefore citric acid] would not be an obvious substitute for BZK’s functions.”
Unclaimed Function, Critical Importance: In making its decision, the court makes an important leap that is critical for its decision — namely that the role or function of citric acid in the claimed invention is as an absorption enhancer and surfactant. The claims do not require that functionality. However, the court determined that the citric acid actually serves as a substitute for BZK and therefore its addition will only be obvious if it would have been obvious as a substitute for BZK.
Once framed as a question of substitution, the court then looked to the prior art and found that the role of citric acid in the prior art was only vaguely known and therefore could support a decision that it would have been obvious to substitute citric acid for the BZK functionality. A separate prior art reference used citric acid in a nasal compound (like Fortical), but included a statement that the citric acid was “not used as an absorption enhancing agent” but instead only as a buffer. That reference also suggests that citric acid would not be an acceptable absorption agent.
In addition, the prior art used different concentration levels of citric acid and only non-human mammalian tests — factors that tend to disrupt any obviousness argument.
Summary Judgment of Nonobviousness Affirmed.
Notes from around the patently-o-sphere:
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Kevin Noonan writes that “the decision provides a contrast between how the Court views chemical obviousness for pharmaceutical formulations today, and the views contained in the Court’s opinion in Pfizer, Inc. v. Apotex, Inc.”
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Aaron Barkoff notes that the opinion aligns the obviousness analysis for formulation claims (for known compounds) with that of claims for novel compounds.
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Ryan Alley writes that “I get the feeling the case is pushing the boundaries of nonobviousness a little too far.”
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Patent Hawk writes that in this case, the “CAFC set its own formula for chemical obviousness”
And before I get branded a naysayer on this case, let me reemphasize that my understanding of this case as a stronger limitation on the obviousness doctrine than we’ve seen recently stems from the specific facts here. Particularly, note that the ‘315 patent reference teaches using 20 mM citric acid in calcitonin nasal sprays. I would understand any improved bioavailability (recited or not) underpinning the nonobviousness of the citric acid substitution to be inherent in the ‘315 patent reference.
Another provision of the new bill that is a potential inovation retartive fraud is the new university IP requisioning policy. Its either fraud outright or needs clarification with reguards to how the property is delt with and the inventors rights to retention of his property and compensation. clearly it would be in the best intrests of everyone to have these institutions involved in development as it is the training format for aspiring ip reaserchers and developers. So the best solution would be competative bidding for consignments including independants subject to reposession and reassignment if unsuscessfull. of course I already have this option available including special order or patent pending with no takers so far. only thiefs sneaking off with it wanting to fight 15year legal battles. This leads us to another problem of lack of enforcement provisions in new legislation and the 40 different other methods of IP theft not corrected in this legislation.
I am not one for obviousness rejections because they retard innovation and allow stolen product usage. In situations like these I think you have to go back to the original invention the nostral sprayer and look at the original chemical compound that should have had a 20 year patent without patents being granted on intervening compounds. After that the original ingrediants may be added to or subtracted and a patent granted on any combination and let the consumer choose the best product this would have been my invention here and also antihistimine inhaler.
They probably want to find it obvious for policy reasons… a bit backwards way of arriving at a decision, of course.
characteristics resulting from an element do not need to be recited in the claim, this is a mistake Examiner’s often make when they attempt to require the applicant to recite secondary considerations in a claim. Charactersitics including those inherent which are disclosed in the spec or by submitted evidence must be considered by the Examiners as per MPEP requirements.
In re Klein did not even reference KSR.
I assume the purpose was disclosed
That is my understanding as well.
Well Ned, I’m not going to review this non-case again, and my memory is hazy. Iirc, the addition of one of the components served two purposes neither of which was claimed, but both of which were disclosed. Indeed, that was part of the research the inventors did iirc.
If that answers your question then good.
Malcolm, 6, what is Dennis trying the say about “unclaimed purpose?” I assume the purposed was disclosed and not later discovered, as it was in the protein case where the importance of one string was not known until well after the patent application being filed.
Fed. Cir. decisons on 103 unobviousness over combined references seem to me to be so fact-dependent and panel-member-dependent as to not be very useful indications of general trends that will control decisions of other panels in other cases. Not just here, but especially in the recent In re Klein, No. 10-1411, 2011 WL 2178134 (Fed. Cir. June 6, 2011), where the Federal Circuit sided with the patent applicant and rejected the Board’s obviousness conclusions, holding that none of the five cited prior art references could be considered “analogous art.” Some of the pre-KSR cases that panel relied on may well not carry that much weight in another panel decision chosing to rely more on relevant statements in KSR. Especially for cases in which the “invention” [not just the claims] may not seem as valuable, contributive, or otherwise attractive.
“Seems like at the least you could rely on the totality of all the factors.”
Seems like at the least you could rely on the totality of all the factors in every determination of obviousness/non-obviousness. Now if we could just get the examiners to do that we’d really have something.
” I would understand any improved bioavailability (recited or not) underpinning the nonobviousness of the citric acid substitution to be inherent in the ‘315 patent reference.”
That may well be true, I can’t be bothered to read all the references and make all the factual findings anew myself. If the CAFC messed up a factual finding then so be it.
Also note though that there were additional factors for non-obviousness in this case they seemed to say. Seems like at the least you could rely on the totality of all the factors.
Thanks Ryan – I saw your blog for the first time today. Great work!
Thanks for the link DC!
And before I get branded a naysayer on this case, let me reemphasize that my understanding of this case as a stronger limitation on the obviousness doctrine than we’ve seen recently stems from the specific facts here. Particularly, note that the ‘315 patent reference teaches using 20 mM citric acid in calcitonin nasal sprays. I would understand any improved bioavailability (recited or not) underpinning the nonobviousness of the citric acid substitution to be inherent in the ‘315 patent reference.
I can accept the recited combination may very well be nonobvious based on other ingredients, or if it were a closed claim, but relying on the citric acid swap-in alone for nonobviousness seems pretty border-pushing to me.
Hindsight attacks on validity have increasingly been rejected by the CAFC recently especially when based on unreasonable combinations of references. This is only one of a number of decisions in point. If common sense as in KSR applies at the litigation stage it should also apply within the USPTO and dubious objections based on prior art that would never realistically be considered together except with hindsight of the invention should be curtailed. Spurious objections cost the inventing community precious development finds, and examiners in the US and elsewhere should be mindful of this fact.
“Such a holding is no generic holding. You gotta take these things on a case by case basis.”
Huh? What? You mean this decision doesn’t have “universal” applicability, like all the decisions you cite but don’t understand?
Lulz
The new Classen case is much more interesting …
After reading this decision I felt like it was just a waste of my time. Simple non-obviousness conclusion reached with very easy to understand and strong support of the kind that has been used for ages.
“The claims do not require that functionality. ”
Who gives a dam? They recited the amount. WHICH IS MORE IMPORTANT BTW.
This decision involved no “leap”, everyone does this every day if they know what they’re doing.
“However, the court determined that the citric acid actually serves as a substitute for BZK and therefore its addition will only be obvious if it would have been obvious as a substitute for BZK. ”
That’s only for that specific combination though. Such a holding is no generic holding. You gotta take these things on a case by case basis. It’s not rocket science.
One critical reading of this case is that the Federal Circuit intends to continue to take steps to ensure that important chemical formulation patents are considered valid.
What is the meaning of the term “important” in this context? Is Unigene’s alternate formulation far better than Novartis’ formulation? Was it ever believed that Novartis’ formulation was the only formulation that would ever work? When it was first revealed, was Unigene’s formulation hailed as a major advance over prior art nasal formulations generally?
I do agree that the panel here (Rader, Moore, O’Malley) seemed desperate to find Unigene’s formulation non-obvious. I’m not sure why. I expect that non-generic drug companies who invest or have invested great amounts of money on reformulating their drugs in order to extend their market lifetimes will be citing this case frequently.
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