Patent Law

Patent Contraceptive

By Gary Odom and Jordan Kuhn

The danger lurking in obviousness is hindsight reasoning. A breakthrough becomes predictable. In hindsight, you/they/whoever should have seen it coming. Bayer's oral contraceptive, Yasmin^®, had unexpected performance. The active ingredient, drospirenone, readily degraded in an acidic environment like the stomach. Grinding it to itty bits, i.e. micronizing, should have exacerbated the problem. So, logically, you'd coat it, to try to make more of the drug bio-available. Bayer found out that coating wasn't necessary, and micronizing didn't decimate bioavailability in an acidic environment nearly as badly as previously thought. That much was obvious. But only in hindsight.

Bayer v. Barr (CAFC 2008-1282)

Barr provoked Bayer by filing to produce a generic version of the drug. Barr convinced the district court to find Bayer's patented compound, via 6,787,531, obvious.

Because the use of drospirenone with 17α-ethinylestradiol as an oral contraceptive was known prior art, Bayer represented that the innovation was to micronize the drospirenone to increase its bioavailability, and that the micronized drospirenone would absorb with a normal pill, against the teachings of the prior art. The district court analyzed the prior art and determined that micronizing drospirenone was taught, and that using a normal pill would have been obvious to try.

Obzilla sat in at the CAFC too, whispering convincingly in two judges' ears (Mayer & Friedman). Only the sensible sourpuss Judge Newman found the big lug of obviousness stinking up the joint with loose logical connections. But let's not get ahead of the joke with the punch line just yet. First, copious case law.

A patent may not be obtained if the differences between the subject matter sought to be patented and the prior art are such that 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 to which the subject matter pertains. 35 U.S.C. § 103(a). An obviousness analysis is based on several factual inquiries. A court must examine the scope and content of the prior art, the differences between the prior art and the claims at issue, and the level of ordinary skill in the pertinent art. Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966). At that point, a court may consider secondary objective evidence of non-obviousness, such as commercial success, long felt but unsolved need, failure of others, and the like. Id.

In KSR, the Supreme Court stated that an invention may be found obvious if it would have been obvious to a person having ordinary skill to try a course of conduct:

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. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.

550 U.S. at 421. This approach is consistent with our methodology in In re O'Farrell, 853 F.2d 894 (Fed. Cir. 1988). See Procter & Gamble Co. v Teva Pharms. USA, Inc., 566 F.3d 989, 996-97 (Fed. Cir. 2009); In re Kubin, 561 F.3d 1351, 1359, (Fed. Cir. 2009). O'Farrell observed that most inventions that are obvious were also obvious to try, but found two classes where that rule of thumb did not obtain.

First, an invention would not have been obvious to try when the inventor would have had to try all possibilities in a field unreduced by direction of the prior art. When "what would have been 'obvious to try' would have been to vary all parameters or try each of numerous possible choices until one possibly arrived at a successful result, where 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" an invention would not have been obvious. O'Farrell, 853 F.2d at 903. This is another way to express the KSR prong requiring the field of search to be among a "finite number of identified" solutions. 550 U.S. at 421; see also Procter & Gamble, 566 F.3d at 996; Kubin, 561 F.3d at 1359. It is also consistent with our interpretation that KSR requires the number of options to be "small or easily traversed." Ortho-McNeil Pharm., Inc. v. Mylan Labs., Inc., 520 F.3d 1358, 1364 (Fed. Cir. 2008).

Second, an invention is not obvious to try where vague prior art does not guide an inventor toward a particular solution. A finding of obviousness would not obtain where "what was 'obvious to try' was to explore a new technology or general approach that seemed to be a promising field of experimentation, where the prior art gave only general guidance as to the particular form of the claimed invention or how to achieve it." O'Farrell, 853 F.2d at 903. This expresses the same idea as the KSR requirement that the identified solutions be "predictable." 550 U.S. at 421; see also Procter & Gamble, 566 F.3d at 996-97; Kubin, 561 F.3d at 1359-60.

Here's how the panel majority boiled the situation down.

At this point, a person having ordinary skill in the art has reached a crossroads where he must choose between two known options: delivery of micronized drospirenone by a normal pill following the spirorenone analogy in the Krause series, or delivery of drospirenone by an enteric-coated pill following the Nickisch teaching that the drug needs to be protected from the stomach. This is a finite number of identified, predictable solutions. See KSR. 550 U.S. at 421. The prior art would have funneled the formulator toward these two options; he would not have been required to try all possibilities in a field unreduced by the prior art, thus avoiding the first pitfall of O'Farrell, 853 F.2d at 903. Additionally, the prior art was not vague in pointing toward a general approach or area of exploration, but rather guided the formulator precisely to the use of either a normal pill or an enteric-coated pill, thus avoiding the second pitfall of O'Farrell. Id. Because the selection of micronized drospirenone in a normal pill led to the result anticipated by the Krause series, the invention would have been obvious. See KSR, 550 U.S. at 421.

Affirmed.

Every time one reads a Newman dissent, one is left wondering how a decision could have gone any other way. A condescending sneer to her lesser colleagues on the court wears no disguise, only the wispy undergarment of "respectful" dissent. A thing of beauty, Judge Newman's sense of rectitude in disgust. Here we are again.

The evidence showed, without contradiction, that it was known that micronized drospirenone rapidly degraded at the acidity of stomach acid. The evidence showed, without contradiction, that the Bayer scientists working in this field believed that the product required an enteric coating in order to prevent degradation in the stomach, upon ingestion as an oral contraceptive. Yet my colleagues, employing their own expertise, hold that since the scientists working in this field turned out to be mistaken, it would have been obvious that it was not necessary to take steps to prevent acid degradation. The court discounts the testimony of the scientists themselves, ignores the knowledge concerning this product and its instability in acid, ignores the textbook teachings, and finds that this unlikely process obviously should have been tried. That is not the law of obviousness.

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, despite the years of contrary belief among the scientists charged with the project. At the time that the Bayer scientists were attempting to formulate drospirenone as an oral contraceptive, the textbook teaching was that micronizing acid-sensitive products would accelerate their acid-induced degradation. See, e.g., Aulton's Pharmaceutics: The Design and Manufacture of Medicines (advising against micronizing acid-sensitive drugs because it reduces the drug's bioavailability). My colleagues criticize these specialists, and rule that it was nonetheless obvious to conduct experiments that they believed would not work. The court rules that the scientists should have "tried" that which they believed would fail, and that when they eventually did try this unlikely formulation, and it succeeded, it was obvious to do so.

The unusual physiological behavior of drospirenone in the stomach was not known; this knowledge followed as scientific explanation; it did not precede the invention in suit. There was no evidence to reasonably suggest that micronized drospirenone was likely to be usable, with 99+ percent consistency of effectiveness, without any protection from degradation by stomach acid. A usable contraceptive requires virtually complete effectiveness, and the standard confronting the Bayer scientists was high. Unlike the unrelated drugs cited by the panel majority, contraceptives require complete effectiveness. Previously known oral contraceptives such as progesterone and spironolactone are not acid sensitive, and drospirenone presented a highly specific challenge to the formulation scientists. The Bayer scientists believed that the way of avoiding the known acid degradation of drospirenone was to protect it from acid. My colleagues, however, find that it would have been obvious to expose it to acid, although it was not obvious to the scientists working on the project.

"Obviousness" requires that the subject matter was obvious to persons of ordinary skill in the field of the invention. The law does not hold it "obvious to try" experiments that contravene conventional knowledge, and that are not deemed reasonably likely to succeed. The evidence in this case is a better measure of obviousness than is the hindsight science of judges, for the scientists who eventually made this discovery testified, without dispute, that they did not believe an uncoated micronized product would meet the demanding criteria of contraceptive effectiveness. The Court in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007) explained that the standard for "obvious to try" is whether there was a "reasonable expectation of success" at the time. It was undisputed that there was not. It was undisputed that it was not reasonably expected that uncoated micronized drospirenone would be 99+% effective as an oral contraceptive when ingested into the acidic stomach, when it was known to degrade rapidly in acid.

The district court stated that micronization was a "viable" option, and that although success was "uncertain," the invention was obvious to try. However, "viability" is not the standard. "Viability" implies that the experiment may or may not succeed. What the law requires is not guesswork, not dumb luck, but a reasonable degree of predictability of success. My colleagues depart from the statutory standard, in ruling that persons of ordinary skill would have conducted experiments that were expected to fail. Nothing in the prior art teaches the likelihood of success of ingestion of uncoated micronized drospirenone; what is taught is the likelihood of failure.

The invention must be viewed as a whole. With the existing knowledge that drospirenone is both hydrophobic and that it degrades rapidly in acid, and the existing knowledge that micronization, although useful to counteract a drug's hydrophobic properties, renders the drug even more susceptible to acid degradation, it was not shown that a person of ordinary skill in this field would have had a reasonable expectation of achieving complete contraceptive bioavailability and effectiveness with uncoated micronized drospirenone. The contrary view has surfaced only in this litigation-induced argument. The exercise of judicial expertise to override the clear evidence of how persons of skill in this field actually behaved, is inappropriate.

I respectfully dissent.

Full post as published by The Patent Prospector on August 07, 2009 (boomark / email).