Unigene Laboratories v. Apotex (CAFC 2010-1006) precedential; Judges Rader (author), Moore, O'Malley

Unigene's drug, Fortical, is a bioequivalent to Novartis' Miacalcin nasal spray. "Unigene developed Fortical® as an alternative to Miacalcin®." Which is to say that Unigene deviated enough from the original formulation to get a patent and cash in, but without having to go through the rigorous drug testing process required of new drugs. This is cunning, but not invention (contrary to the CAFC's weasel words that it might be). This is "the sport of kings," that only large corporations can play.

Creating a bioequivalent of Miacalin® would allow approval of the new pharmaceutical liquid dosage form as an ANDA under 21 U.S.C. § 355(j)(2)(A)(vii) or an NDA under 21 U.S.C. § 505(b)(2)-- both enjoying the additional advantage of using the clinical data or literature submitted in support of Miacalcin®. Alternatively, a composition requiring full clinical trials to demonstrate safety and effectiveness would require approval as an NDA under 35 U.S.C. § 505(b)(1), a significantly longer process. This court appreciates that the Hatch-Waxman Act encourages and rewards replication of protected compounds in some circumstances--an activity that rarely, but can, lead to innovative products.

Unigene alleged inequitable conduct, which didn't fly. But then, neither did the 40 pieces of prior art Unigene submitted as rendering '392 obvious. No guessing who the party in favor was - the deck was stacked, as usual. The CAFC backed the district court on a case that closed in summary judgment.

This court reviews the district court's grant of summary judgment without deference. Eisai Co. Ltd. v. Dr. Reddy's Labs., 533 F.3d 1353, 1356 (Fed. Cir. 2008). Summary judgment is appropriate if the movant can show both the absence of genuine issues of material fact and entitlement to judgment as a matter of law. Fed. R. Civ. P. 56(c). This court reviews the evidence in the light most favorable to the party opposing the motion, with all doubts resolved in favor of the nonmovant. Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, 1360-61 (Fed. Cir. 2008).

Obviousness under 35 U.S.C. § 103(a) is a legal question based on underlying factual determinations. Eisai, 533 F.3d at 1356 (citing Richardson-Vicks Inc. v. Upjohn Co., 122 F.3d 1478, 1479 (Fed. Cir. 1997)). An obviousness analysis measures the difference between the claimed invention and the prior art to determine whether "the subject matter as a whole would have been obvious at the time the invention was made" to a person having ordinary skill in the art. Alza Corp. v. Mylan Labs., Inc., 464 F.3d 1286, 1289 (Fed. Cir. 2006) (citing In re Kahn, 441 F.3d 977, 985 (Fed. Cir. 2006)). The factual underpinnings, often referred to as the Graham factors, include 1) the scope and content of the prior art; 2) the level of ordinary skill in the art; 3) the differences between the claimed invention and the prior art; and 4) evidence of secondary factors, also known as objective indicia of nonobviousness. Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966).

Here's the CAFC studiously brushing past obvious-to-try.

Obviousness requires more than a mere showing that the prior art includes separate references covering each separate limitation in a claim under examination. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 418 (2007). Rather, obviousness requires the additional showing that a person of ordinary skill at the time of the invention would have selected and combined those prior art elements in the normal course of research and development to yield the claimed invention. Id. at 421 (describing that a person of ordinary skill possesses "ordinary creativity, [and is] not an automaton"); see also Bayer Schering Pharm. AG v. Barr Labs., Inc., 575 F.3d 1341, 1350 (Fed. Cir. 2009) (Newman, J., dissenting) ("The statutory criterion is whether the invention would have been obvious to persons of ordinary skill at the time of the invention, not whether it is sufficiently simple to appear obvious to judges after the discovery is finally made . . . .").

A person of ordinary skill at the time of the invention interprets the prior art using common sense and appropriate perspective. KSR, 550 U.S. at 421. In KSR the Supreme Court observed:

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.

Id. Accordingly, when design need and market pressure may dictate a commonsensical path using a finite number of identified predictable solutions to one of ordinary skill, deviations from that path are likely products of innovation.

For this ruling, the CAFC reverts to its old, stiff, old teaching-suggestion-motivation (TSM) test, which largely got overturned by the Supreme Court as "inflexible." The high Court proffered instead the subjective "obvious-to-try," which meant that if there was any sense to trying something, it would be obvious.

This court has observed that teachings from prior art, suggestions beyond the literal teachings of those art references, or even motivations from the store of common knowledge of one of ordinary skill in the art field ("TSM")--flexibly viewed and applied--provide the sources of evidence that an ordinary skilled artisan might have found and combined at the time of the invention. Ortho-McNeil, 520 F.3d at 1364-65 ("[A] flexible TSM test remains the primary guarantor against a non-statutory hindsight analysis . . . ."); see also KSR, 550 U.S. at 419 ("The obviousness analysis cannot be confined by a formalistic conception of the words, teachings, suggestion, and motivation, or by overemphasis on the importance of published articles and the explicit content of issued patents.").

In this case, the patent claims a new composition or formulation to deliver an FDA-approved active ingredient. Thus, the claimed invention is not obvious if a person of ordinary skill would not select and combine the prior art references to reach the claimed composition or formulation. Eli Lilly v. Zenith Goldline Pharm., 471 F.3d 1369, 1380 (Fed. Cir. 2006) ("to establish a prima facie case of obviousness based on a combination of elements in the prior art, the law requires a motivation to select the references and to combine them in the particular claimed manner to reach the claimed invention").

To render a claim obvious, prior art cannot be "vague" and must collectively, although not explicitly, guide an artisan of ordinary skill towards a particular solution. Bayer Schering., 575 F.3d at 1347. Indeed, "most inventions that are obvious were also obvious to try," id., and a combination is only obvious to try if a person of ordinary skill has "a good reason to pursue the known options." KSR, 550 U.S. at 421. When a field is "unreduced by direction of the prior art," and when prior art gives "no indication of which parameters were critical or no direction as to which of many possible choices is likely to be successful," an invention is not obvious to try. Bayer Schering, 575 F.3d at 1347 (citing O'Farrell, 853 F.2d at 903); see also Ortho-McNeil, 520 F.3d at 1364 (stating the number of options must be "small or easily traversed").

More specific to chemical compounds, which actually points to finding obviousness in this case, but of course doesn't when factoring in court bias -

A prima facie case of obviousness in the chemical arts is often based on a known compound, called a "lead compound," which serves as a starting point for a person of ordinary skill developing the claimed invention. See Eisai, 533 F.3d at 1357. Where the patent at issue claims a chemical compound, a lead compound is often used to show structural similarities between the claimed compound and prior art. Id. (citing Eli Lilly, 471 F.3d at 1377). In the context of a composition or formulation patent where the patented formulation was made to mimic a previously FDA-approved formulation, the functional and pharmaceutical properties of the "lead compound" can be more relevant than the actual chemical structure (though not always mutually exclusive). Thus, the term "reference composition" is more appropriate than "lead compound" when considering obviousness for a chemical composition that the infringer deliberately imitates.

The courts found insufficient "reason or motivation" to put together compounds that would have been obvious to try, as Apotex demonstrated. The supposed magic ingredient was citric acid, which was known to enhance bio-absorption.

Thus, the "about 20.0 mM citric acid" limitation alone supports the district court's grant of summary judgment of nonobviousness. When used as an absorption enhancer in the '116 patent, citric acid was one of over fifty options. See KSR, 550 U.S. at 421. Further, when the prior art used citric acid at about 20 mM, as in the '315 patent, it was used only as a buffer. There is no genuine dispute of material fact that a person of ordinary skill attempting to make a liquid composition to deliver salmon calcitonin into a human body through nasal administration, would not have considered using about 20 mM citric acid with the narrowly claimed amounts of benzyl alcohol, phenylethyl alcohol, and polysorbate 80, because the formulation would not be expected to perform properly to meet the specificity of a pharmaceutical use. Thus, even accepting that there was a design need and market pressure to develop a pharmaceutical formulation that is bioequivalent to Miacalcin®, there is no evidence in the record that claim 19 would be an obvious solution to those motivations.

Affirmed.

More conflicting precedent that gives more leeway to rule however a court wants, as long as it facilely sounds sensible.